The July issue of Acta Physiologica contains a beautiful example of how experimental biology provides new insights into the important topic of oral reception and subsequent perception of fatty substances in mammals. In the paper “Fatty acid taste quality information via GPR40 and CD36 in the posterior tongue of mice,” Nagai and colleagues [1] skillfully performed surgical experiments, that, combined with additional behavioral tests shed new light on the circuitry of fatty acid signaling in the mouth. The paper contains observations that easily could have been missed if less attention would have been paid to details. The authors reach the tempting (and debatable) conclusion that long-chain fatty acids (LCFA), at least for mice, taste like sweet and/or umami tastants.
In an earlier paper by the same group, also published in Acta Physiologica [2], electrophysiological measurements on single chorda tympani nerve fibers coming from the anterior tongue were performed on wildtype mice and knockout mice that lack the G protein-coupled receptor GPR120, also known as free fatty acid receptor 4 (FFAR4). GPR120 is one of the proteins that have been identified about two decades ago [3, 4] to be involved in fatty acid tasting, together with other proteins, including the G protein-coupled receptor GPR40, also known as free fatty acid receptor 1 (FFAR1) and the LCFA transporter CD36 (“cluster of differentiation 36”) [see [5] for a review]. These three proteins have very diverse roles in different organs and tissues. Both GPR120 and GPR40 function in pancreatic insulin signaling, and act as the prime receptors in the gut-brain axis of fatty acid signaling that determine the long-term “wanting” of high energy nutrients like sugars and fat [6]. Those functions are but a few examples of many for GPR120 and GPR40. CD36, on the other hand, is the high affinity transporter needed to import the fuel into demanding tissues such as the cardiac muscle, a tissue that mainly relies on the mitochondrial oxidation of LCFA for energy generation. CD36 also has many other functions [3, 5].
Whether the taste of fat (by sensing of LCFA that result from oral lipase actions on triglycerides) should be considered as the sixth taste modality (next to sweet, bitter, umami, salt and sour) has long been debated, but much evidence from experimental biology pleads for it. The specific term “oleogustus” has been coined [7] to provide a word that is easily recognized as pertaining to the taste of oily or fatty substances without referring to other sensations of fat perception, like texture and viscosity. Indeed, humans are quite capable of tasting free fatty acids of different chain lengths. Short-chain fatty acids taste sour, medium-chain fatty acids are experienced as irritants, and LCFA taste differently than any of the other basic modalities. LCFA are described as unpalatable [
{"title":"Tongue in Cheek: A Sweet and/or Umami Taste for Fatty Acids","authors":"Feike R. van der Leij","doi":"10.1111/apha.70088","DOIUrl":"https://doi.org/10.1111/apha.70088","url":null,"abstract":"<p>The July issue of <i>Acta Physiologica</i> contains a beautiful example of how experimental biology provides new insights into the important topic of oral reception and subsequent perception of fatty substances in mammals. In the paper “Fatty acid taste quality information via GPR40 and CD36 in the posterior tongue of mice,” Nagai and colleagues [<span>1</span>] skillfully performed surgical experiments, that, combined with additional behavioral tests shed new light on the circuitry of fatty acid signaling in the mouth. The paper contains observations that easily could have been missed if less attention would have been paid to details. The authors reach the tempting (and debatable) conclusion that long-chain fatty acids (LCFA), at least for mice, taste like sweet and/or umami tastants.</p><p>In an earlier paper by the same group, also published in Acta Physiologica [<span>2</span>], electrophysiological measurements on single chorda tympani nerve fibers coming from the anterior tongue were performed on wildtype mice and knockout mice that lack the G protein-coupled receptor GPR120, also known as free fatty acid receptor 4 (FFAR4). GPR120 is one of the proteins that have been identified about two decades ago [<span>3, 4</span>] to be involved in fatty acid tasting, together with other proteins, including the G protein-coupled receptor GPR40, also known as free fatty acid receptor 1 (FFAR1) and the LCFA transporter CD36 (“cluster of differentiation 36”) [see [<span>5</span>] for a review]. These three proteins have very diverse roles in different organs and tissues. Both GPR120 and GPR40 function in pancreatic insulin signaling, and act as the prime receptors in the gut-brain axis of fatty acid signaling that determine the long-term “wanting” of high energy nutrients like sugars and fat [<span>6</span>]. Those functions are but a few examples of many for GPR120 and GPR40. CD36, on the other hand, is the high affinity transporter needed to import the fuel into demanding tissues such as the cardiac muscle, a tissue that mainly relies on the mitochondrial oxidation of LCFA for energy generation. CD36 also has many other functions [<span>3, 5</span>].</p><p>Whether the taste of fat (by sensing of LCFA that result from oral lipase actions on triglycerides) should be considered as the sixth taste modality (next to sweet, bitter, umami, salt and sour) has long been debated, but much evidence from experimental biology pleads for it. The specific term “oleogustus” has been coined [<span>7</span>] to provide a word that is easily recognized as pertaining to the taste of oily or fatty substances without referring to other sensations of fat perception, like texture and viscosity. Indeed, humans are quite capable of tasting free fatty acids of different chain lengths. Short-chain fatty acids taste sour, medium-chain fatty acids are experienced as irritants, and LCFA taste differently than any of the other basic modalities. LCFA are described as unpalatable [","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>The airway surface liquid (ASL), which lines the luminal surface of the lung, is a complex layer containing mucins that trap inhaled particles and a liquid layer that supports ciliary function, that also contains antimicrobial peptides, proteins, and metabolites generated by the epithelial cells, inflammatory cells, and the resident lung microbiota. Precise regulation of ASL composition protects the pulmonary tissue from the external environment and is critical for a healthy lung.</p><p>Much is known about the identity and function of the airway epithelial ion channels and transporters that contribute to the regulation of ASL volume and mucus clearance. Nucleotides and nucleosides in the ASL modify fluid volume through receptor-mediatedion transport mechanisms [<span>1</span>], while bacterial metabolites are sensed by taste receptors in the ciliated and chemosensory cells of the airway and initiate protective reflexes [<span>2</span>].</p><p>Intermediary metabolites of glucose, such as lactate and pyruvate, as well as short chain fatty acids, are often elevated in the ASL during disease, and can render the lung more susceptible to infection and/or inflammation [<span>3</span>]. The increased abundance of ASL metabolites is associated with changes in cellular synthesis and transport [<span>4</span>]. The production and secretion of L-lactate into the ASL increase during hyperglycaemia, in the presence of bacteria and inflammation [<span>5, 6</span>]. The role of the H<sup>+</sup>-coupled monocarboxylate transporters (e.g., SLC16A1, 7 and 3; MCT1, 2 and 4 respectively) in the secretion of such metabolites, including into the ASL, has been reported [<span>5, 7</span>]. But is this a one-way process? Are metabolites also removed from the ASL and if so, how? A recent editorial and manuscript in Acta Physiologica highlighted new views on the shuttling of lactate from cell to cell and tissue to tissue as a proposed energy source, supporting both its secretion and uptake [<span>8, 9</span>]. But until now, there has been little documented evidence for transporters that enable the uptake of metabolites across the lumen of the airway and could play a role in the regulation of ASL metabolite concentration.</p><p>A new manuscript in Acta Physiologica, by Guenquen et al. [<span>10</span>] has changed that. The authors found that the Na<sup>+</sup>-coupled monocarboxylate transporter SLC5A8 (SMCT1) was highly expressed in mouse trachea and in human bronchial epithelial cultures. SLC5A8 is a member of a family that also includes more well-known Na<sup>+</sup>-coupled glucose transporters, such as SLC5A1 (SGLT1). These transporters can utilize the Na<sup>+</sup> gradient established by the epithelial Na<sup>+</sup>/K<sup>+</sup>-ATPase to drive uptake into the cell in the absence of a substrate gradient. As highlighted by Guenquen and colleagues, SLC5A8 has previously attracted attention as a tumor suppressor in several tissues (including the lung) and has b
{"title":"The SLC58A Na+-Monocarboxylate Transporter—Can It Scavenge Lung Metabolites to Prevent Airway Infections?","authors":"Deborah Baines, Robert Tarran","doi":"10.1111/apha.70086","DOIUrl":"https://doi.org/10.1111/apha.70086","url":null,"abstract":"<p>The airway surface liquid (ASL), which lines the luminal surface of the lung, is a complex layer containing mucins that trap inhaled particles and a liquid layer that supports ciliary function, that also contains antimicrobial peptides, proteins, and metabolites generated by the epithelial cells, inflammatory cells, and the resident lung microbiota. Precise regulation of ASL composition protects the pulmonary tissue from the external environment and is critical for a healthy lung.</p><p>Much is known about the identity and function of the airway epithelial ion channels and transporters that contribute to the regulation of ASL volume and mucus clearance. Nucleotides and nucleosides in the ASL modify fluid volume through receptor-mediatedion transport mechanisms [<span>1</span>], while bacterial metabolites are sensed by taste receptors in the ciliated and chemosensory cells of the airway and initiate protective reflexes [<span>2</span>].</p><p>Intermediary metabolites of glucose, such as lactate and pyruvate, as well as short chain fatty acids, are often elevated in the ASL during disease, and can render the lung more susceptible to infection and/or inflammation [<span>3</span>]. The increased abundance of ASL metabolites is associated with changes in cellular synthesis and transport [<span>4</span>]. The production and secretion of L-lactate into the ASL increase during hyperglycaemia, in the presence of bacteria and inflammation [<span>5, 6</span>]. The role of the H<sup>+</sup>-coupled monocarboxylate transporters (e.g., SLC16A1, 7 and 3; MCT1, 2 and 4 respectively) in the secretion of such metabolites, including into the ASL, has been reported [<span>5, 7</span>]. But is this a one-way process? Are metabolites also removed from the ASL and if so, how? A recent editorial and manuscript in Acta Physiologica highlighted new views on the shuttling of lactate from cell to cell and tissue to tissue as a proposed energy source, supporting both its secretion and uptake [<span>8, 9</span>]. But until now, there has been little documented evidence for transporters that enable the uptake of metabolites across the lumen of the airway and could play a role in the regulation of ASL metabolite concentration.</p><p>A new manuscript in Acta Physiologica, by Guenquen et al. [<span>10</span>] has changed that. The authors found that the Na<sup>+</sup>-coupled monocarboxylate transporter SLC5A8 (SMCT1) was highly expressed in mouse trachea and in human bronchial epithelial cultures. SLC5A8 is a member of a family that also includes more well-known Na<sup>+</sup>-coupled glucose transporters, such as SLC5A1 (SGLT1). These transporters can utilize the Na<sup>+</sup> gradient established by the epithelial Na<sup>+</sup>/K<sup>+</sup>-ATPase to drive uptake into the cell in the absence of a substrate gradient. As highlighted by Guenquen and colleagues, SLC5A8 has previously attracted attention as a tumor suppressor in several tissues (including the lung) and has b","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tendons are fibrous tissues connecting muscles to bones, providing joint stability and enabling movement. Adaptor proteins regulate cellular processes essential for maintaining tendon function. Phosphotyrosine-binding domain-containing engulfment adaptor protein 1 (GULP1) participates in multiple cellular activities; however, its specific role in tendons remains unclear. This study aims to investigate the expression and function of GULP1 in tendons using Gulp1 knockout (KO) mice.
Methods
Motor behavior and limb muscle strength were evaluated using gait analysis, footprint tracking, ledge walking, hindlimb clasping, and the hanging wire test. Protein and mRNA expression levels were assessed using Western blot and quantitative real-time PCR, respectively. Histological analysis was performed on patellar and Achilles tendons, with BrdU labeling for cell proliferation assessment. Primary tail tendon fibroblasts were analyzed, and collagen fibril diameter distribution was measured using transmission electron microscopy (TEM).
Results
Gulp1 KO mice exhibited impaired motor coordination characterized by abnormal gait, reduced limb strength, and poor balance, including shorter stride and stance lengths, along with greater sway length. GULP1 expression was higher in tendons than in other tissues. Gulp1 KO mice exhibited reduced Achilles tendon thickness, decreased tendon cell proliferation, diminished ERK1/2 phosphorylation, and reduced colony formation in primary tendon cells. Expression of tendon-specific genes (Scleraxis, Mohawk, and type I collagen) was downregulated in Gulp1 KO mice. TEM analysis revealed smaller collagen fibril diameters and disrupted fibrillogenesis in Gulp1 KO mice.
Conclusion
GULP1 plays a critical role in tendon cell proliferation, differentiation, and collagen fibrillogenesis, which are essential for maintaining tendon structure and function.
{"title":"GULP1 Regulates Tendon Cell Proliferation and Maturation Essential for Motor Coordination in Mice","authors":"Na Rae Park, Seong-Hwan Kim, Jung-Eun Kim","doi":"10.1111/apha.70087","DOIUrl":"https://doi.org/10.1111/apha.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Tendons are fibrous tissues connecting muscles to bones, providing joint stability and enabling movement. Adaptor proteins regulate cellular processes essential for maintaining tendon function. Phosphotyrosine-binding domain-containing engulfment adaptor protein 1 (GULP1) participates in multiple cellular activities; however, its specific role in tendons remains unclear. This study aims to investigate the expression and function of GULP1 in tendons using <i>Gulp1</i> knockout (KO) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Motor behavior and limb muscle strength were evaluated using gait analysis, footprint tracking, ledge walking, hindlimb clasping, and the hanging wire test. Protein and mRNA expression levels were assessed using Western blot and quantitative real-time PCR, respectively. Histological analysis was performed on patellar and Achilles tendons, with BrdU labeling for cell proliferation assessment. Primary tail tendon fibroblasts were analyzed, and collagen fibril diameter distribution was measured using transmission electron microscopy (TEM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Gulp1</i> KO mice exhibited impaired motor coordination characterized by abnormal gait, reduced limb strength, and poor balance, including shorter stride and stance lengths, along with greater sway length. GULP1 expression was higher in tendons than in other tissues. <i>Gulp1</i> KO mice exhibited reduced Achilles tendon thickness, decreased tendon cell proliferation, diminished ERK1/2 phosphorylation, and reduced colony formation in primary tendon cells. Expression of tendon-specific genes (<i>Scleraxis</i>, <i>Mohawk</i>, and <i>type I collagen</i>) was downregulated in <i>Gulp1</i> KO mice. TEM analysis revealed smaller collagen fibril diameters and disrupted fibrillogenesis in <i>Gulp1</i> KO mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GULP1 plays a critical role in tendon cell proliferation, differentiation, and collagen fibrillogenesis, which are essential for maintaining tendon structure and function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabela P. Leirão, Pedro L. Katayama, Daniel B. Zoccal
Aim
Exposure to low oxygen (hypoxia) or high carbon dioxide levels (hypercapnia) leads to a compensatory increase in pulmonary ventilation. Among the motor changes supporting the respiratory responses is the recruitment of abdominal expiratory muscles (ABD), which can enhance expiratory airflow or alter the duration of the expiratory phase. In this study, we assessed the impact of ABD recruitment on metabolic, motor, and ventilatory parameters in unanesthetized, freely behaving animals.
Methods
Sprague–Dawley Holtzman male adult rats (n = 7) were instrumented to perform simultaneous recordings of pulmonary ventilation, body temperature, diaphragmatic and ABD activities, and O2 consumption during exposure (20–30 min) to various levels of hypoxia (12%–8% O2) and hypercapnia (3%–7% CO2).
Results
Hypoxia or hypercapnia exposure evoked active expiration (AE); however, ABD recruitment did not occur during the entire exposure period, displaying an intermittent profile. The occurrence of AE during hypoxia and hypercapnia conditions was linked to additional increases in tidal volume when compared to periods without ABD activity (p < 0.05) and showed no associations with changes in diaphragmatic burst amplitude. Analyses of flow-like patterns suggested that AE during hypoxia recruited expiratory reserve volume during late expiration, while under hypercapnia, it accelerated lung emptying and increased the expiratory flow peak during post-inspiration. AE was also associated with increased oxygen consumption and did not improve air convection requirement.
Conclusion
AE enhances pulmonary ventilation during hypoxia and hypercapnia primarily by increasing tidal volume. However, this motor behavior may also affect other mechanical aspects of the respiratory system to improve alveolar ventilation and gas exchange.
{"title":"Respiratory and Metabolic Effects of Active Expiration in Freely Behaving Rats","authors":"Isabela P. Leirão, Pedro L. Katayama, Daniel B. Zoccal","doi":"10.1111/apha.70084","DOIUrl":"https://doi.org/10.1111/apha.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Exposure to low oxygen (hypoxia) or high carbon dioxide levels (hypercapnia) leads to a compensatory increase in pulmonary ventilation. Among the motor changes supporting the respiratory responses is the recruitment of abdominal expiratory muscles (ABD), which can enhance expiratory airflow or alter the duration of the expiratory phase. In this study, we assessed the impact of ABD recruitment on metabolic, motor, and ventilatory parameters in unanesthetized, freely behaving animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sprague–Dawley Holtzman male adult rats (<i>n</i> = 7) were instrumented to perform simultaneous recordings of pulmonary ventilation, body temperature, diaphragmatic and ABD activities, and O<sub>2</sub> consumption during exposure (20–30 min) to various levels of hypoxia (12%–8% O<sub>2</sub>) and hypercapnia (3%–7% CO<sub>2</sub>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia or hypercapnia exposure evoked active expiration (AE); however, ABD recruitment did not occur during the entire exposure period, displaying an intermittent profile. The occurrence of AE during hypoxia and hypercapnia conditions was linked to additional increases in tidal volume when compared to periods without ABD activity (<i>p</i> < 0.05) and showed no associations with changes in diaphragmatic burst amplitude. Analyses of flow-like patterns suggested that AE during hypoxia recruited expiratory reserve volume during late expiration, while under hypercapnia, it accelerated lung emptying and increased the expiratory flow peak during post-inspiration. AE was also associated with increased oxygen consumption and did not improve air convection requirement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AE enhances pulmonary ventilation during hypoxia and hypercapnia primarily by increasing tidal volume. However, this motor behavior may also affect other mechanical aspects of the respiratory system to improve alveolar ventilation and gas exchange.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabela Aparecida Divino, Ana Laura da Vieira-da-Silva, Marcos Vinicius Esteca, Rafael Paschini Tonon, Felipe Oliveira Gomes da Cruz, Renata Rosseto Braga, Eduardo Rochete Ropelle, Paulo Guimarães Gandra, Igor Luchini Baptista
Aim
This work aimed to investigate the effects of the loss of Parkin in middle-aged mice skeletal muscle, focusing on different types of myofibers and in the analysis of proteins related to protein synthesis and degradation as well as the analysis of force generation and motor balance.
Methods
We used male mice C57BL/6J (WT) and Parkin knockout mice, Parkintm1Shn (Parkin−/−) at 3 and 10 months of age. We used Walking Beam, Open Field, Spider Mice and Maximum Power Tests to assess motor, balance, and endurance functions. We used flexor digitorum brevis (FDB) muscle for force generation analysis, and tibial anterior (TA) and soleus (SOL) muscles were used for biomolecular techniques because of their difference in fiber type. These muscles were used to investigate markers of protein synthesis and degradation, mitochondrial respiration, and myofiber diameter.
Results
The Absence of Parkin in middle-aged mice leads to a reduction in isometric force generation but maintained overall motor and locomotion abilities, exhibited only minor balance deficits. In the SOL muscle of middle-aged Parkin−/− mice, we observed a reduction of muscle mass and myofiber diameter, also a significant decrease in mitochondrial respiratory capacity and Complex V. In the same group, we observed a reduction in the phosphorylation of AKT and 4E-BP1, and an increase in MURF-1 while Ubiquitin K63 levels decreased. We did not observe relevant differences in the TA muscle.
Conclusion
Our results suggest middle-aged Parkin−/− mice exhibited muscle atrophy and mitochondrial dysfunction primarily in oxidative myofibers before noticeable motor dysfunction occurs.
{"title":"Absence of Parkin Results in Atrophy of Oxidative Myofibers and Modulation of AKT and MURF1 Signaling in Middle-Aged Male Mice","authors":"Isabela Aparecida Divino, Ana Laura da Vieira-da-Silva, Marcos Vinicius Esteca, Rafael Paschini Tonon, Felipe Oliveira Gomes da Cruz, Renata Rosseto Braga, Eduardo Rochete Ropelle, Paulo Guimarães Gandra, Igor Luchini Baptista","doi":"10.1111/apha.70082","DOIUrl":"https://doi.org/10.1111/apha.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This work aimed to investigate the effects of the loss of Parkin in middle-aged mice skeletal muscle, focusing on different types of myofibers and in the analysis of proteins related to protein synthesis and degradation as well as the analysis of force generation and motor balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used male mice C57BL/6J (WT) and Parkin knockout mice, Parkintm1Shn (Parkin<sup>−/−</sup>) at 3 and 10 months of age. We used Walking Beam, Open Field, Spider Mice and Maximum Power Tests to assess motor, balance, and endurance functions. We used flexor digitorum brevis (FDB) muscle for force generation analysis, and tibial anterior (TA) and soleus (SOL) muscles were used for biomolecular techniques because of their difference in fiber type. These muscles were used to investigate markers of protein synthesis and degradation, mitochondrial respiration, and myofiber diameter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Absence of Parkin in middle-aged mice leads to a reduction in isometric force generation but maintained overall motor and locomotion abilities, exhibited only minor balance deficits. In the SOL muscle of middle-aged Parkin<sup>−/−</sup> mice, we observed a reduction of muscle mass and myofiber diameter, also a significant decrease in mitochondrial respiratory capacity and Complex V. In the same group, we observed a reduction in the phosphorylation of AKT and 4E-BP1, and an increase in <i>MURF-1</i> while Ubiquitin K63 levels decreased. We did not observe relevant differences in the TA muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest middle-aged Parkin<sup>−/−</sup> mice exhibited muscle atrophy and mitochondrial dysfunction primarily in oxidative myofibers before noticeable motor dysfunction occurs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Podocytes, highly specialized epithelial cells located in the glomerulus of the kidney, are essential to the filtration barrier that ensures separation of blood and urine. These cells exhibit a unique architecture, characterized by an intricate network of foot processes interconnected by slit diaphragms, which serve as a critical selective filter for plasma ultrafiltration.
This review focusses on synthesizing current knowledge on podocyte physiology, emphasizing the roles of key proteins, signaling pathways, and environmental factors that influence their function.
Methods
Publications featuring current advances in molecular biology and imaging techniques were used to summarize new insights into the regulatory pathways governing podocyte homeostasis, as well as the mechanisms of injury and repair.
Results
The biology of podocytes encompasses diverse processes, including cytoskeletal dynamics, cellular signaling, and interactions with neighboring cells and the extracellular matrix. Disruption of podocyte structure or function is fundamental to a variety of glomerular diseases, which can lead to proteinuria and progressive kidney failure.
Conclusion
Understanding the intricate mechanisms involved in maintaining podocyte homeostasis offers potential therapeutic strategies to protect and restore podocyte integrity, addressing a critical need in nephrology. By highlighting the intricate balance required for podocyte survival, we reinforce their significance as both a cornerstone of renal filtration and a focal point in kidney disease research.
{"title":"The Life of a Kidney Podocyte","authors":"Desiree Loreth, Wiebke Sachs, Catherine Meyer-Schwesinger","doi":"10.1111/apha.70081","DOIUrl":"https://doi.org/10.1111/apha.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Podocytes, highly specialized epithelial cells located in the glomerulus of the kidney, are essential to the filtration barrier that ensures separation of blood and urine. These cells exhibit a unique architecture, characterized by an intricate network of foot processes interconnected by slit diaphragms, which serve as a critical selective filter for plasma ultrafiltration.</p>\u0000 \u0000 <p>This review focusses on synthesizing current knowledge on podocyte physiology, emphasizing the roles of key proteins, signaling pathways, and environmental factors that influence their function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Publications featuring current advances in molecular biology and imaging techniques were used to summarize new insights into the regulatory pathways governing podocyte homeostasis, as well as the mechanisms of injury and repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The biology of podocytes encompasses diverse processes, including cytoskeletal dynamics, cellular signaling, and interactions with neighboring cells and the extracellular matrix. Disruption of podocyte structure or function is fundamental to a variety of glomerular diseases, which can lead to proteinuria and progressive kidney failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Understanding the intricate mechanisms involved in maintaining podocyte homeostasis offers potential therapeutic strategies to protect and restore podocyte integrity, addressing a critical need in nephrology. By highlighting the intricate balance required for podocyte survival, we reinforce their significance as both a cornerstone of renal filtration and a focal point in kidney disease research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew T. Lewis, Fabio G. Laginestra, Jesse C. Craig, Markus Amann, Russell S. Richardson, Robert W. Wiseman, Ryan M. Broxterman
Aim
Distinguish the relative importance of intramuscular acidosis (hydrogen ion) and inorganic phosphate in skeletal muscle fatigue in vivo in rats.
Methods
We used direct sciatic nerve electrical stimulations to evoke twitches at different frequencies of contraction (0.25-, 0.50-, 0.75-, 1-, 2-, and 4-Hz) in the triceps surae to impose a range of intramuscular metabolic perturbations, quantified by phosphorus nuclear magnetic resonance spectroscopy. Linear mixed-effects models were used to analyze the relationships between peak twitch force and intramuscular hydrogen ion or inorganic phosphate concentration (as Z-scores) during the protocols that decreased peak twitch force (2- and 4-Hz).
Results
Although intramuscular hydrogen ion and inorganic phosphate concentrations increased with increasing frequencies of contraction, peak twitch force did not begin to decrease until a “threshold” inorganic phosphate concentration was reached. A given hydrogen ion accumulation was associated with a greater decrease in peak twitch force during 4-Hz compared to 2-Hz (β: −1.19 vs. −0.62, p < 0.001). In contrast, the decrease in peak twitch force for a given inorganic phosphate accumulation was not different between 4- and 2-Hz (β: −0.89 vs. −0.85, p = 0.889).
Conclusions
The inconsistent relationship between the decrease in twitch force and intramuscular hydrogen ion accumulation is not congruent with the primary mechanisms by which acidosis is thought to mediate muscle fatigue. In contrast, the discernible twitch force–inorganic phosphate breakpoint and the consistent relationship between the decrease in twitch force and intramuscular inorganic phosphate accumulation are congruent with the concept of a critical concentration beyond which inorganic phosphate mediates muscle fatigue.
目的探讨肌内酸中毒（氢离子）与无机磷酸盐在大鼠体内骨骼肌疲劳中的相对作用。方法使用直接坐骨神经电刺激引起三头肌表面不同频率的抽搐（0.25-,0.50-,0.75-,1-，2-和4-Hz），施加一系列肌内代谢扰动，用磷核磁共振波谱法量化。使用线性混合效应模型来分析在降低峰值抽动力（2 hz和4 hz）的方案中，峰值抽动力与肌内氢离子或无机磷酸盐浓度（作为z分数）之间的关系。结果肌内氢离子和无机磷酸盐浓度随着收缩频率的增加而增加，但抽搐力峰值直到无机磷酸盐浓度达到“阈值”时才开始下降。与2 hz相比，给定的氢离子积累与4 hz时峰值抽动力的更大下降有关（β: - 1.19 vs. - 0.62, p < 0.001）。相比之下，给定无机磷酸盐积累的峰值收缩力的下降在4 hz和2 hz之间没有差异（β: - 0.89 vs. - 0.85, p = 0.889）。结论抽搐力下降与肌内氢离子积累之间的不一致关系与酸中毒介导肌肉疲劳的主要机制不一致。相反，可识别的抽搐力-无机磷酸盐断点以及抽搐力下降与肌内无机磷酸盐积累之间的一致关系与无机磷酸盐调节肌肉疲劳的临界浓度的概念一致。
{"title":"Skeletal Muscle Fatigue in Rats Is More Consistently Related to Increased Inorganic Phosphate Concentration Than Acidosis","authors":"Matthew T. Lewis, Fabio G. Laginestra, Jesse C. Craig, Markus Amann, Russell S. Richardson, Robert W. Wiseman, Ryan M. Broxterman","doi":"10.1111/apha.70083","DOIUrl":"https://doi.org/10.1111/apha.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Distinguish the relative importance of intramuscular acidosis (hydrogen ion) and inorganic phosphate in skeletal muscle fatigue in vivo in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used direct sciatic nerve electrical stimulations to evoke twitches at different frequencies of contraction (0.25-, 0.50-, 0.75-, 1-, 2-, and 4-Hz) in the triceps surae to impose a range of intramuscular metabolic perturbations, quantified by phosphorus nuclear magnetic resonance spectroscopy. Linear mixed-effects models were used to analyze the relationships between peak twitch force and intramuscular hydrogen ion or inorganic phosphate concentration (as <i>Z</i>-scores) during the protocols that decreased peak twitch force (2- and 4-Hz).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although intramuscular hydrogen ion and inorganic phosphate concentrations increased with increasing frequencies of contraction, peak twitch force did not begin to decrease until a “threshold” inorganic phosphate concentration was reached. A given hydrogen ion accumulation was associated with a greater decrease in peak twitch force during 4-Hz compared to 2-Hz (<i>β</i>: −1.19 vs. −0.62, <i>p</i> < 0.001). In contrast, the decrease in peak twitch force for a given inorganic phosphate accumulation was not different between 4- and 2-Hz (<i>β</i>: −0.89 vs. −0.85, <i>p</i> = 0.889).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The inconsistent relationship between the decrease in twitch force and intramuscular hydrogen ion accumulation is not congruent with the primary mechanisms by which acidosis is thought to mediate muscle fatigue. In contrast, the discernible twitch force–inorganic phosphate breakpoint and the consistent relationship between the decrease in twitch force and intramuscular inorganic phosphate accumulation are congruent with the concept of a critical concentration beyond which inorganic phosphate mediates muscle fatigue.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rollssman de Oliveira Cavalheiro, Fernanda Brognara, Carlos Alberto Aguiar da Silva, Jaci Airton Castania, Carlos Augusto Fernandes Molina, David Murphy, Minna Moreira Dias Romano, Helio Cesar Salgado
Aim
To evaluate the effect of carotid sinus nerve stimulation (CSNS) in the progression of cardiorenal syndrome type 1 (CRS1), 3 days after acute myocardial infarction (AMI).
Methods
Male rats were divided into four groups. CSNS was applied daily for 10 min over 3 days. Cardiac, renal, and inflammatory parameters characterized the CRS1 and the electroceutical effects of CSNS.
Results
CSNS reduced the ischemic zone compared to the AMI group not exposed to CSNS (32.7% ± 2.2% vs. 8.0% ± 1.8%). Heart rate (bpm) was increased in the AMI group, showing 440 ± 7.6 at 48 h and 428 ± 1.0 at 60 h post-AMI. Additionally, arterial pressure (mmHg) was increased in the AMI group at 48 h, as follows: mean: 98 ± 1.7, diastolic: 89 ± 2.1, and systolic: 122 ± 5.3. In contrast, the CSNS + AMI group showed significant reductions of these parameters: mean: 79 ± 2.0, diastolic, 66 ± 1.7, and systolic: 99 ± 2.7. Renal injury was confirmed by increased apoptosis in the AMI group. A significant increase in TNF-α was observed in both heart and kidneys (pg/mg of tissue) in the AMI group and reduced IL-6 and IL-1β levels in the CSNS + AMI group, indicating an attenuation of the inflammatory responses by CSNS.
Conclusions
This study demonstrates early cardiac and renal dysfunction in CRS1 following AMI, associated with elevated inflammatory markers (TNF-α, IL-6, and IL-1β) and renal apoptosis. Therefore, CSNS appears to be a promising electroceutical approach for CRS1. Besides, on the basis of previous studies from our laboratory, CSNS involves stimulation of the baroreflex, activating the parasympathetic and inhibiting the sympathetic nervous system.
{"title":"Activation of the Carotid Sinus Nerve After Acute Myocardial Infarction in a Cardiorenal Syndrome Type 1 Model in Sprague–Dawley Rats","authors":"Rollssman de Oliveira Cavalheiro, Fernanda Brognara, Carlos Alberto Aguiar da Silva, Jaci Airton Castania, Carlos Augusto Fernandes Molina, David Murphy, Minna Moreira Dias Romano, Helio Cesar Salgado","doi":"10.1111/apha.70076","DOIUrl":"https://doi.org/10.1111/apha.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the effect of carotid sinus nerve stimulation (CSNS) in the progression of cardiorenal syndrome type 1 (CRS1), 3 days after acute myocardial infarction (AMI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male rats were divided into four groups. CSNS was applied daily for 10 min over 3 days. Cardiac, renal, and inflammatory parameters characterized the CRS1 and the electroceutical effects of CSNS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CSNS reduced the ischemic zone compared to the AMI group not exposed to CSNS (32.7% ± 2.2% vs. 8.0% ± 1.8%). Heart rate (bpm) was increased in the AMI group, showing 440 ± 7.6 at 48 h and 428 ± 1.0 at 60 h post-AMI. Additionally, arterial pressure (mmHg) was increased in the AMI group at 48 h, as follows: mean: 98 ± 1.7, diastolic: 89 ± 2.1, and systolic: 122 ± 5.3. In contrast, the CSNS + AMI group showed significant reductions of these parameters: mean: 79 ± 2.0, diastolic, 66 ± 1.7, and systolic: 99 ± 2.7. Renal injury was confirmed by increased apoptosis in the AMI group. A significant increase in TNF-α was observed in both heart and kidneys (pg/mg of tissue) in the AMI group and reduced IL-6 and IL-1β levels in the CSNS + AMI group, indicating an attenuation of the inflammatory responses by CSNS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates early cardiac and renal dysfunction in CRS1 following AMI, associated with elevated inflammatory markers (TNF-α, IL-6, and IL-1β) and renal apoptosis. Therefore, CSNS appears to be a promising electroceutical approach for CRS1. Besides, on the basis of previous studies from our laboratory, CSNS involves stimulation of the baroreflex, activating the parasympathetic and inhibiting the sympathetic nervous system.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinpeng Wang, Site Xu, Yuchuan Xue, Kaicheng Wen, Mingzhe Sun, Lin Tao
Background
Bone is a dynamic tissue undergoing constant remodeling mediated by osteoblasts and osteoclasts. An imbalance between these cells can lead to reduced bone mass, disrupted microarchitecture, and ultimately osteoporosis. O-GlcNAcylation is a dynamic and reversible posttranslational modification where uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is added or removed from serine/threonine residues of proteins by OGT and OGA, respectively. Emerging evidence indicates that appropriate O-GlcNAcylation is essential for bone remodeling, although its specific effects remain controversial.
Aims
This review aims to summarize the process of O-GlcNAcylation and critically evaluate its specific effects on osteoblast-mediated and osteoclast-mediated bone remodeling.
Materials & Methods
Based on a comprehensive analysis of published scientific literature, we synthesized the current evidence regarding the role of O-GlcNAcylation in bone cell differentiation and function, and its association with osteoporosis.
Results
Our analysis reveals that cellular demands for O-GlcNAcylation vary during osteoblastic and osteoclastic differentiation. Moderate O-GlcNAcylation is essential for osteoblast differentiation, whereas dynamic alterations in O-GlcNAcylation are crucial for osteoclast differentiation. Furthermore, elevated O-GlcNAcylation levels are consistently observed in both primary and secondary osteoporosis cases, suggesting a potential pathogenic role in the dysregulation of bone remodeling.
Discussion
These findings indicate that the effects of O-GlcNAcylation are cell type- and differentiation stage-dependent in bone. The observed elevation of O-GlcNAcylation in osteoporosis underscores its potential contribution to the dysregulation of bone remodeling pathways.
Conclusion
This review provides novel mechanistic insights into osteoporosis pathogenesis via dysregulation of the O-GlcNAcylation post-translational modification. Understanding these mechanisms will facilitate the development of novel therapeutic strategies targeting O-GlcNAcylation to restore balanced bone remodeling.
{"title":"Emerging Roles of Protein O-GlcNAcylation in Bone Remodeling: New Insights Into Osteoporosis","authors":"Jinpeng Wang, Site Xu, Yuchuan Xue, Kaicheng Wen, Mingzhe Sun, Lin Tao","doi":"10.1111/apha.70080","DOIUrl":"https://doi.org/10.1111/apha.70080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bone is a dynamic tissue undergoing constant remodeling mediated by osteoblasts and osteoclasts. An imbalance between these cells can lead to reduced bone mass, disrupted microarchitecture, and ultimately osteoporosis. O-GlcNAcylation is a dynamic and reversible posttranslational modification where uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is added or removed from serine/threonine residues of proteins by OGT and OGA, respectively. Emerging evidence indicates that appropriate O-GlcNAcylation is essential for bone remodeling, although its specific effects remain controversial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review aims to summarize the process of O-GlcNAcylation and critically evaluate its specific effects on osteoblast-mediated and osteoclast-mediated bone remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>Based on a comprehensive analysis of published scientific literature, we synthesized the current evidence regarding the role of O-GlcNAcylation in bone cell differentiation and function, and its association with osteoporosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis reveals that cellular demands for O-GlcNAcylation vary during osteoblastic and osteoclastic differentiation. Moderate O-GlcNAcylation is essential for osteoblast differentiation, whereas dynamic alterations in O-GlcNAcylation are crucial for osteoclast differentiation. Furthermore, elevated O-GlcNAcylation levels are consistently observed in both primary and secondary osteoporosis cases, suggesting a potential pathogenic role in the dysregulation of bone remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>These findings indicate that the effects of O-GlcNAcylation are cell type- and differentiation stage-dependent in bone. The observed elevation of O-GlcNAcylation in osteoporosis underscores its potential contribution to the dysregulation of bone remodeling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review provides novel mechanistic insights into osteoporosis pathogenesis via dysregulation of the O-GlcNAcylation post-translational modification. Understanding these mechanisms will facilitate the development of novel therapeutic strategies targeting O-GlcNAcylation to restore balanced bone remodeling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This essay recounts and revisits the scientific contributions of Christian Bohr, highlighting his pivotal role in discovering allostery about 120 years ago. Bohr's meticulous experimentation led to identifying two distinct forms of allostery: homotropic (single-ligand) and heterotropic (multi-ligand), the latter widely recognized as the Bohr Effect. His insights into oxygen binding to hemoglobin, as also modulated by carbon dioxide presence, laid the foundation for part of modern pharmacological advancements. Today, allosteric principles drive drug development, improving specificity and potentially minimizing adverse effects, with numerous allosteric modulators emerging in pharmaceutical pipelines. The treatise spans 13 chapters and an appendix with definitions on allosteric terms. It begins with Bohr's background, laboratory environment, and pivotal experiments in 1903 that demonstrated allosteric mechanisms. It traces Bohr's scientific journey—from medical training to his professorship in Copenhagen—and his collaborative research with Karl Hasselbalch and August Krogh. The work situates Bohr within the broader historical context, examining influence of earlier, 19th-century, and later physicochemical and physiological thoughts on his discoveries. Further chapters discuss dose-response relationships, including Hüfner's hyperbolic equation and Henri's enzyme kinetics, parallel to Bohr's findings. Bohr's S-shaped oxygen-hemoglobin binding curve, analyzed in 1904, marked a critical advancement in understanding homotropic allostery. Subsequent developments, such as Hill's equation and the Monod-Wyman-Changeux model, settled both types of allostery description. My study concludes with Bohr's abandonment in 1910 of his secretion theory and his legacy. Despite his early death in 1911, Bohr's contributions remain fundamental, warranting revitalized recognition for his discovery of allostery.
{"title":"Christian Bohr. Discoverer of Homotropic and Heterotopic Allostery","authors":"Niels Bindslev","doi":"10.1111/apha.70016","DOIUrl":"https://doi.org/10.1111/apha.70016","url":null,"abstract":"<p>This essay recounts and revisits the scientific contributions of Christian Bohr, highlighting his pivotal role in discovering allostery about 120 years ago. Bohr's meticulous experimentation led to identifying two distinct forms of allostery: homotropic (single-ligand) and heterotropic (multi-ligand), the latter widely recognized as the Bohr Effect. His insights into oxygen binding to hemoglobin, as also modulated by carbon dioxide presence, laid the foundation for part of modern pharmacological advancements. Today, allosteric principles drive drug development, improving specificity and potentially minimizing adverse effects, with numerous allosteric modulators emerging in pharmaceutical pipelines. The treatise spans 13 chapters and an appendix with definitions on allosteric terms. It begins with Bohr's background, laboratory environment, and pivotal experiments in 1903 that demonstrated allosteric mechanisms. It traces Bohr's scientific journey—from medical training to his professorship in Copenhagen—and his collaborative research with Karl Hasselbalch and August Krogh. The work situates Bohr within the broader historical context, examining influence of earlier, 19th-century, and later physicochemical and physiological thoughts on his discoveries. Further chapters discuss dose-response relationships, including Hüfner's hyperbolic equation and Henri's enzyme kinetics, parallel to Bohr's findings. Bohr's S-shaped oxygen-hemoglobin binding curve, analyzed in 1904, marked a critical advancement in understanding homotropic allostery. Subsequent developments, such as Hill's equation and the Monod-Wyman-Changeux model, settled both types of allostery description. My study concludes with Bohr's abandonment in 1910 of his secretion theory and his legacy. Despite his early death in 1911, Bohr's contributions remain fundamental, warranting revitalized recognition for his discovery of allostery.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S734","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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