P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson’s trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1β, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.
P2X7受体(P2X7R)在炎症和纤维化过程中起着重要的调节作用,但祖传三针(ST36)是否能通过调节P2X7R抑制炎症和纤维化的研究还很有限。给野生型小鼠和 P2X7R 基因敲除小鼠皮下注射异丙肾上腺素 5 毫克/千克,连续 7 天;治疗组在 ST36 处接受电针刺激(EA),连续 7 个疗程。治疗 7 个疗程后,对小鼠进行马森氏三色染色以评估纤维化情况。通过形态学、心电图和超声心动图评估心脏功能和结构。为了描述 ST36 对炎症的影响,研究人员进行了 Western 印迹、苏木精和伊红染色、免疫组化、炎症细胞因子生化分析和透射电子显微镜检查。P2X7R 在 ISO 处理的小鼠中过表达。与 ISO 组的小鼠相比,ST36 点的 EA(而非非点的 EA)可减少 ISO 诱导的心脏纤维化、HW/BW 和 R+S 波的增加。此外,ST36 点的 EA 还能降低 ISO 在心室中上调的 P2X7R 和 NLRP3。此外,EA还降低了血清中的细胞因子IL-1β、IL-6和IL-18,抑制了泡沫细胞聚集、炎症细胞浸润和自噬。然而,ST36 EA 未能减轻 P2X7R 基因敲除小鼠的心脏纤维化和肥大。总之,ST36 位置的 EA 可通过 P2X7R 减轻 ISO 诱导的纤维化。
{"title":"P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult","authors":"Ting Zhang, Jing Lv, Zhong-yue Liu, Qiu-lian Lei, Ze-fei Jiang, Xiao-xiang Sun, Xing Yue, Xuan Li, Ke-li Zhu, Yun-kuan Yang, Ling Luo, Xin Cao","doi":"10.1007/s11302-024-10009-y","DOIUrl":"https://doi.org/10.1007/s11302-024-10009-y","url":null,"abstract":"<p>P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson’s trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1β, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140811103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-20DOI: 10.1007/s11302-024-10007-0
Jun Liu, Ting-Ting Liu, Lan Mou, Yuwen Zhang, Xiang Chen, Qi Wang, Bin-Lu Deng, Jie Liu
In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5’-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.
{"title":"P2X7 receptor: a potential target for treating comorbid anxiety and depression","authors":"Jun Liu, Ting-Ting Liu, Lan Mou, Yuwen Zhang, Xiang Chen, Qi Wang, Bin-Lu Deng, Jie Liu","doi":"10.1007/s11302-024-10007-0","DOIUrl":"https://doi.org/10.1007/s11302-024-10007-0","url":null,"abstract":"<p>In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5’-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.1007/s11302-024-10008-z
V. S. Alves, Fabiana Cristina-Rodrigues, R. Coutinho-Silva
{"title":"The P2Y2 receptor as a sensor of nucleotides and cell recruitment during inflammatory processes of the liver.","authors":"V. S. Alves, Fabiana Cristina-Rodrigues, R. Coutinho-Silva","doi":"10.1007/s11302-024-10008-z","DOIUrl":"https://doi.org/10.1007/s11302-024-10008-z","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140693498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1007/s11302-024-10006-1
José R. Cruz-Muñoz, Eduardo E. Valdez-Morales, Alma Barajas-Espinosa, Tonatiuh Barrios-García, Andrómeda Liñán-Rico, Raquel Guerrero-Alba
Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1β mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.
{"title":"Gene expression alterations of purinergic signaling components in obesity-associated intestinal low-grade inflammation in type 2 diabetes","authors":"José R. Cruz-Muñoz, Eduardo E. Valdez-Morales, Alma Barajas-Espinosa, Tonatiuh Barrios-García, Andrómeda Liñán-Rico, Raquel Guerrero-Alba","doi":"10.1007/s11302-024-10006-1","DOIUrl":"https://doi.org/10.1007/s11302-024-10006-1","url":null,"abstract":"<p>Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1β mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-03-21DOI: 10.1007/s11302-023-09934-1
Antonio R Artalejo, Marina Arribas-Blázquez, María Victoria Barahona, Celia Llorente-Sáez, Luis Alcides Olivos-Oré
María Teresa Miras Portugal devoted most of her scientific life to the study of purinergic signalling. In an important part of her work, she used a model system: the chromaffin cells of the adrenal medulla. It was in these cells that she identified diadenosine polyphosphates, from which she proceeded to the study of adrenomedullary purinome: nucleotide synthesis and degradation, adenosine transport, nucleotide uptake into chromaffin granules, exocytotic release of nucleotides and autocrine regulation of chromaffin cell function via purinoceptors. This short review will focus on the current state of knowledge of the purinoceptors of adrenal chromaffin cells, a subject to which María Teresa made seminal contributions and which she continued to study until the end of her scientific life.
{"title":"María Teresa Miras Portugal: a pioneer in the study of purinoceptors in chromaffin cells.","authors":"Antonio R Artalejo, Marina Arribas-Blázquez, María Victoria Barahona, Celia Llorente-Sáez, Luis Alcides Olivos-Oré","doi":"10.1007/s11302-023-09934-1","DOIUrl":"10.1007/s11302-023-09934-1","url":null,"abstract":"<p><p>María Teresa Miras Portugal devoted most of her scientific life to the study of purinergic signalling. In an important part of her work, she used a model system: the chromaffin cells of the adrenal medulla. It was in these cells that she identified diadenosine polyphosphates, from which she proceeded to the study of adrenomedullary purinome: nucleotide synthesis and degradation, adenosine transport, nucleotide uptake into chromaffin granules, exocytotic release of nucleotides and autocrine regulation of chromaffin cell function via purinoceptors. This short review will focus on the current state of knowledge of the purinoceptors of adrenal chromaffin cells, a subject to which María Teresa made seminal contributions and which she continued to study until the end of her scientific life.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9514040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chromaffin granules are secretory granules present in adrenal medulla chromaffin cells. They contain high contents of catecholamines and nucleotides and have been regarded as a model system for the study of vesicular transmitter uptake and release. In 1988, Dr. María Teresa Miras Portugal, when studying catecholamine biosynthesis, detected a novel group of nucleotides, the diadenosine polyphosphates, in the adrenal chromaffin granules. Based on this finding, she unraveled the existence of diadenosine polyphosphate-mediated chemical transmission, leading to a paradigm shift in the field of purinergic signaling. She is also a pioneer in the studies on vesicular nucleotide storage. First, María Teresa and her group characterized nucleotide transport in chromaffin granules and synaptic vesicles using fluorescent nucleotide derivatives such as 1, N6-ethenoadenosine triphosphates. Then, they revealed the presence of a hypothetical vesicular nucleotide transporter with unique properties in terms of substrate specificity. In this article, we will describe her contributions to vesicular nucleotide storage and the foundations she laid for future studies.
{"title":"María Teresa Miras Portugal: a pioneer for vesicular nucleotide storage.","authors":"Yoshinori Moriyama, Nao Hasuzawa, Masatoshi Nomura","doi":"10.1007/s11302-022-09912-z","DOIUrl":"10.1007/s11302-022-09912-z","url":null,"abstract":"<p><p>Chromaffin granules are secretory granules present in adrenal medulla chromaffin cells. They contain high contents of catecholamines and nucleotides and have been regarded as a model system for the study of vesicular transmitter uptake and release. In 1988, Dr. María Teresa Miras Portugal, when studying catecholamine biosynthesis, detected a novel group of nucleotides, the diadenosine polyphosphates, in the adrenal chromaffin granules. Based on this finding, she unraveled the existence of diadenosine polyphosphate-mediated chemical transmission, leading to a paradigm shift in the field of purinergic signaling. She is also a pioneer in the studies on vesicular nucleotide storage. First, María Teresa and her group characterized nucleotide transport in chromaffin granules and synaptic vesicles using fluorescent nucleotide derivatives such as 1, N6-ethenoadenosine triphosphates. Then, they revealed the presence of a hypothetical vesicular nucleotide transporter with unique properties in terms of substrate specificity. In this article, we will describe her contributions to vesicular nucleotide storage and the foundations she laid for future studies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10357275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-02-16DOI: 10.1007/s11302-023-09923-4
Jonathon Smith, Beatriz Gil Lopez-Avila, Tobias Engel, Eva M Jimenez Mateos, Mariana Alves
{"title":"Differently expression of the metabotropic P2Y receptor family after hypoxia-induced seizures in neonates and seizure suppression via P2Y<sub>1</sub> receptor agonism.","authors":"Jonathon Smith, Beatriz Gil Lopez-Avila, Tobias Engel, Eva M Jimenez Mateos, Mariana Alves","doi":"10.1007/s11302-023-09923-4","DOIUrl":"10.1007/s11302-023-09923-4","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10720596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1007/s11302-024-09990-1
Esmerilda Garcia Delicado, Herbert Zimmermann
{"title":"Preface to special issue \"A tribute to Maria Teresa Miras-Portugal\".","authors":"Esmerilda Garcia Delicado, Herbert Zimmermann","doi":"10.1007/s11302-024-09990-1","DOIUrl":"10.1007/s11302-024-09990-1","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The role of extracellular nucleotides as modulators of inflammation and cell stress is well established. One of the main actions of these molecules is mediated by the activation of purinergic receptors (P2) of the plasma membrane. P2 receptors can be classified according to two different structural families: P2X ionotropic ion channel receptors, and P2Y metabotropic G protein-coupled receptors. During inflammation, damaged cells release nucleotides and purinergic signaling occurs along the temporal pattern of the synthesis of pro-inflammatory and pro-resolving mediators by myeloid and lymphoid cells. In macrophages under pro-inflammatory conditions, the expression and activity of cyclooxygenase 2 significantly increases and enhances the circulating levels of prostaglandin E2 (PGE2), which exerts its effects both through specific plasma membrane receptors (EP1-EP4) and by activation of intracellular targets. Here we review the mechanisms involved in the crosstalk between PGE2 and P2Y receptors on macrophages, which is dependent on several isoforms of protein kinase C and protein kinase D1. Due to this crosstalk, a P2Y-dependent increase in calcium is blunted by PGE2 whereas, under these conditions, macrophages exhibit reduced migratory capacity along with enhanced phagocytosis, which contributes to the modulation of the inflammatory response and tissue repair.
{"title":"Crosstalk between P2Y receptors and cyclooxygenase activity in inflammation and tissue repair.","authors":"Adrián Povo-Retana, Sergio Sánchez-García, Carlota Alvarez-Lucena, Rodrigo Landauro-Vera, Patricia Prieto, Carmen Delgado, Paloma Martín-Sanz, Lisardo Boscá","doi":"10.1007/s11302-023-09938-x","DOIUrl":"10.1007/s11302-023-09938-x","url":null,"abstract":"<p><p>The role of extracellular nucleotides as modulators of inflammation and cell stress is well established. One of the main actions of these molecules is mediated by the activation of purinergic receptors (P2) of the plasma membrane. P2 receptors can be classified according to two different structural families: P2X ionotropic ion channel receptors, and P2Y metabotropic G protein-coupled receptors. During inflammation, damaged cells release nucleotides and purinergic signaling occurs along the temporal pattern of the synthesis of pro-inflammatory and pro-resolving mediators by myeloid and lymphoid cells. In macrophages under pro-inflammatory conditions, the expression and activity of cyclooxygenase 2 significantly increases and enhances the circulating levels of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), which exerts its effects both through specific plasma membrane receptors (EP1-EP4) and by activation of intracellular targets. Here we review the mechanisms involved in the crosstalk between PGE<sub>2</sub> and P2Y receptors on macrophages, which is dependent on several isoforms of protein kinase C and protein kinase D1. Due to this crosstalk, a P2Y-dependent increase in calcium is blunted by PGE<sub>2</sub> whereas, under these conditions, macrophages exhibit reduced migratory capacity along with enhanced phagocytosis, which contributes to the modulation of the inflammatory response and tissue repair.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9283429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-09-30DOI: 10.1007/s11302-023-09970-x
Juan Carlos Gil-Redondo, María José Queipo, Yaiza Trueba, Celia Llorente-Sáez, Julia Serrano, Felipe Ortega, Rosa Gómez-Villafuertes, Raquel Pérez-Sen, Esmerilda G Delicado
The P2X7 receptor (P2X7R) stands out within the purinergic family as it has exclusive pharmacological and regulatory features, and it fulfills distinct roles depending on the type of stimulation and cellular environment. Tonic activation of P2X7R promotes cell proliferation, whereas sustained activation is associated with cell death. Yet strikingly, prolonged P2X7R activation in rat cerebellar granule neurons and astrocytes does not affect cell survival. The intracellular pathways activated by P2X7Rs involve proteins like MAPKs, ERK1/2 and p38, and interactions with growth factor receptors could explain their behavior in populations of rat cerebellar cells. In this study, we set out to characterize the intracellular mechanisms through which P2X7Rs and Trk receptors, EGFR (epidermal growth factor receptor) and BDNFR (brain-derived neurotrophic factor receptor), regulate the dual-specificity phosphatase DUSP1. In cerebellar astrocytes, the regulation of DUSP1 expression by P2X7R depends on ERK and p38 activation. EGFR stimulation can also induce DUSP1 expression, albeit less strongly than P2X7R. Conversely, EGF was virtually ineffective in regulating DUSP1 in granule neurons, a cell type in which BDNF is the main regulator of DUSP1 expression and P2X7R only induces a mild response. Indeed, the regulation of DUSP1 elicited by BDNF reflects the balance between both transcriptional and post-transcriptional mechanisms. Importantly, when the regulation of DUSP1 expression is compromised, the viability of both astrocytes and neurons is impaired, suggesting this phosphatase is essential to maintain proper cell cytoarchitecture and functioning.
{"title":"DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden.","authors":"Juan Carlos Gil-Redondo, María José Queipo, Yaiza Trueba, Celia Llorente-Sáez, Julia Serrano, Felipe Ortega, Rosa Gómez-Villafuertes, Raquel Pérez-Sen, Esmerilda G Delicado","doi":"10.1007/s11302-023-09970-x","DOIUrl":"10.1007/s11302-023-09970-x","url":null,"abstract":"<p><p>The P2X7 receptor (P2X7R) stands out within the purinergic family as it has exclusive pharmacological and regulatory features, and it fulfills distinct roles depending on the type of stimulation and cellular environment. Tonic activation of P2X7R promotes cell proliferation, whereas sustained activation is associated with cell death. Yet strikingly, prolonged P2X7R activation in rat cerebellar granule neurons and astrocytes does not affect cell survival. The intracellular pathways activated by P2X7Rs involve proteins like MAPKs, ERK1/2 and p38, and interactions with growth factor receptors could explain their behavior in populations of rat cerebellar cells. In this study, we set out to characterize the intracellular mechanisms through which P2X7Rs and Trk receptors, EGFR (epidermal growth factor receptor) and BDNFR (brain-derived neurotrophic factor receptor), regulate the dual-specificity phosphatase DUSP1. In cerebellar astrocytes, the regulation of DUSP1 expression by P2X7R depends on ERK and p38 activation. EGFR stimulation can also induce DUSP1 expression, albeit less strongly than P2X7R. Conversely, EGF was virtually ineffective in regulating DUSP1 in granule neurons, a cell type in which BDNF is the main regulator of DUSP1 expression and P2X7R only induces a mild response. Indeed, the regulation of DUSP1 elicited by BDNF reflects the balance between both transcriptional and post-transcriptional mechanisms. Importantly, when the regulation of DUSP1 expression is compromised, the viability of both astrocytes and neurons is impaired, suggesting this phosphatase is essential to maintain proper cell cytoarchitecture and functioning.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41132149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}