The physiological and biomedical importance of hydrogen sulfide (H 2 S) has been extensively studied in our body. H 2 S can be endogenously produced in a variety of cells and tissues by cystathionine γ-lyase, cystathionine β-synthase, and/or 3-mercaptopyruvate sulfurtransferase, and is involved in the regulation of vascular function, cell growth, insulin secretion, neurotransmission, myocardial contractility, inflammation, and nociception, etc. H 2 S post-translationally modifies proteins by yielding a hydropersulfide moiety (–SSH) in specific cysteine residue(s), termed as S -sulfhydration. It is becoming increasingly recognized that S -sulfhydration is a major sources of H 2 S bioactivity. In this research highlight, we discuss our latest published findings which demonstrate the S -sulfhydration regulation of proteins by H 2 S and their importance in aging and cancer protection.
{"title":"Protein S-sulfhydration as a major sources of H2S bioactivity","authors":"Guangdong Yang","doi":"10.14800/RCI.337","DOIUrl":"https://doi.org/10.14800/RCI.337","url":null,"abstract":"The physiological and biomedical importance of hydrogen sulfide (H 2 S) has been extensively studied in our body. H 2 S can be endogenously produced in a variety of cells and tissues by cystathionine γ-lyase, cystathionine β-synthase, and/or 3-mercaptopyruvate sulfurtransferase, and is involved in the regulation of vascular function, cell growth, insulin secretion, neurotransmission, myocardial contractility, inflammation, and nociception, etc. H 2 S post-translationally modifies proteins by yielding a hydropersulfide moiety (–SSH) in specific cysteine residue(s), termed as S -sulfhydration. It is becoming increasingly recognized that S -sulfhydration is a major sources of H 2 S bioactivity. In this research highlight, we discuss our latest published findings which demonstrate the S -sulfhydration regulation of proteins by H 2 S and their importance in aging and cancer protection.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73997458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hematopoietic stem cell (HSC) aging has been directly linked to the development of several hematological disorders including myeloproliferative diseases. We recently described that in elderly mice (20-month-old), physiological aging of the hematopoietic system is associated with a decreased expression of the Transcription Intermediary Factor 1γ (Tif1γ) gene in HSCs. In young mice (4-month-old), deleted for the Tif1γ gene in HSCs (Tif1γ -/- ), the hematopoiesis aging phenotype is intensified. We discovered that Tif1γ controls the TGF-b receptor 1 (Tgfbr1) and finely regulates the number of myeloid-restricted HSCs in bone marrow. Altogether, we established that young Tif1γ -/- mice develop a phenotype of premature hematopoietic aging, which may explain their tendency to myeloproliferative disease. We identified two populations of HSCs specifically discriminated by Tgfbr1 expression and afforded evidence of the capture of myeloid-restricted (Tgfbr1 hi ) and myeloid-lymphoid-balanced (Tgfbr1 lo ) HSC. In conclusion, our study proves that Tif1γ can regulate the balance between lymphoid and myeloid HSCs, through a modulation of the TGF-b signaling.
{"title":"Tif1γ controls the TGF-β receptor on hematopoietic stem cells: implication in physiological aging","authors":"R. Quéré, J. Bastie, L. Delva","doi":"10.14800/RCI.335","DOIUrl":"https://doi.org/10.14800/RCI.335","url":null,"abstract":"Hematopoietic stem cell (HSC) aging has been directly linked to the development of several hematological disorders including myeloproliferative diseases. We recently described that in elderly mice (20-month-old), physiological aging of the hematopoietic system is associated with a decreased expression of the Transcription Intermediary Factor 1γ (Tif1γ) gene in HSCs. In young mice (4-month-old), deleted for the Tif1γ gene in HSCs (Tif1γ -/- ), the hematopoiesis aging phenotype is intensified. We discovered that Tif1γ controls the TGF-b receptor 1 (Tgfbr1) and finely regulates the number of myeloid-restricted HSCs in bone marrow. Altogether, we established that young Tif1γ -/- mice develop a phenotype of premature hematopoietic aging, which may explain their tendency to myeloproliferative disease. We identified two populations of HSCs specifically discriminated by Tgfbr1 expression and afforded evidence of the capture of myeloid-restricted (Tgfbr1 hi ) and myeloid-lymphoid-balanced (Tgfbr1 lo ) HSC. In conclusion, our study proves that Tif1γ can regulate the balance between lymphoid and myeloid HSCs, through a modulation of the TGF-b signaling.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78715959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) is an adaptor protein required for SLAM family receptor signaling. In T cells, signaling from different SLAM receptors (SLAM-Rs) governs differentiation, effector function, and apoptosis specifically through the self-regulatory program of T cell receptor restimulation-induced cell death (RICD). Indeed, SLAM-R signaling and RICD are impaired in X-linked lymphoproliferative disease (XLP) patients that are deficient for SAP, as well as in SAP-deficient mice. Importantly, defective RICD likely contributes to excessive CD8 + T cell accumulation and severe immunopathology noted in XLP patients upon infection with Epstein-Barr Virus (EBV). It is well established that SAP signaling through different SLAM-Rs is associated with the recruitment of the Src-family kinase FYN. Surprisingly, we recently discovered that FYN has no role in RICD. Instead, our data suggests that SAP enhances the recruitment and activation of LCK to the SLAM family receptor NK, T, and B cell Antigen (NTB-A), and thus amplifies TCR signaling for optimal RICD. In this research highlight we review the role of SAP in T cells and describe our recent findings placing LCK as an important player in SAP-mediated NTB-A signaling for T cell apoptosis.
{"title":"LCK connects NTB-A and SAP signaling in T cells to restimulation-induced cell death","authors":"Gil Katz, Scott M. Krummey, A. Snow","doi":"10.14800/RCI.292","DOIUrl":"https://doi.org/10.14800/RCI.292","url":null,"abstract":"Signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) is an adaptor protein required for SLAM family receptor signaling. In T cells, signaling from different SLAM receptors (SLAM-Rs) governs differentiation, effector function, and apoptosis specifically through the self-regulatory program of T cell receptor restimulation-induced cell death (RICD). Indeed, SLAM-R signaling and RICD are impaired in X-linked lymphoproliferative disease (XLP) patients that are deficient for SAP, as well as in SAP-deficient mice. Importantly, defective RICD likely contributes to excessive CD8 + T cell accumulation and severe immunopathology noted in XLP patients upon infection with Epstein-Barr Virus (EBV). It is well established that SAP signaling through different SLAM-Rs is associated with the recruitment of the Src-family kinase FYN. Surprisingly, we recently discovered that FYN has no role in RICD. Instead, our data suggests that SAP enhances the recruitment and activation of LCK to the SLAM family receptor NK, T, and B cell Antigen (NTB-A), and thus amplifies TCR signaling for optimal RICD. In this research highlight we review the role of SAP in T cells and describe our recent findings placing LCK as an important player in SAP-mediated NTB-A signaling for T cell apoptosis.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75378160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This research highlight focuses on new developments in our understanding of the structure and function of the mammalian dyad, and of the type 2 ryanodine receptor (RyR2) in particular. Recent investigations have challenged the view of dyads as static and repetitive structures with one functioning much as the next. New data has revealed that dyads have diverse molecular architectures and are dynamic structures where the organization of their RyR2 can be changed by changes in the local environment.
{"title":"The Dynamic Dyad: Cardiac Ryanodine Receptors on the Move","authors":"D. Scriven, E. Moore","doi":"10.14800/RCI.267","DOIUrl":"https://doi.org/10.14800/RCI.267","url":null,"abstract":"This research highlight focuses on new developments in our understanding of the structure and function of the mammalian dyad, and of the type 2 ryanodine receptor (RyR2) in particular. Recent investigations have challenged the view of dyads as static and repetitive structures with one functioning much as the next. New data has revealed that dyads have diverse molecular architectures and are dynamic structures where the organization of their RyR2 can be changed by changes in the local environment.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83271183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it develops in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in the ad libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitum -fed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype.
{"title":"The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity","authors":"Christophe Lenglos, J. Calvez, E. Timofeeva","doi":"10.14800/RCI.222","DOIUrl":"https://doi.org/10.14800/RCI.222","url":null,"abstract":"Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it develops in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in the ad libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitum -fed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82791857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Certain cell signaling pharmaceutical targets have the potential to provide substantial clinical benefit when inhibited on some cell types yet elicit unwanted collateral damage when impeded on others. Thus, the appropriate therapeutic strategy for this situation would be to block preferentially receptor activation on the desired cell set. Taking advantage of the clustering within lipid rafts of toll-like receptor 4 (TLR4) and Fc gamma receptors (FcγR) during TLR4 activation, we have identified a mechanism that allows an antibody to block more favorably signaling on leukocytes, cells that underlie acute and chronic inflammatory processes. The anti-TLR4 monoclonal antibody (mAb), Hu 15C1, co-engages TLR4 and FcγRs to enhance its inhibitory potency via an avidity effect on FcγR-bearing cells. This novel mechanism of action allows the mAb to block efficiently TLR4 activation on FcγR-bearing inflammatory cells, while limiting the duration of effect on cells lacking FcγRs. As receptor clustering in lipid rafts is a common phenomenon, this mechanism could be exploited to anchor similar receptor-targeting mAbs or formats bearing an antibody Fc domain to desired cell types.
{"title":"Harnessing receptor clustering in lipid rafts to tailor the inhibitory effects of monoclonal antibodies to specific cell types","authors":"L. Shang, W. Ferlin, M. Kosco-Vilbois, G. Elson","doi":"10.14800/RCI.278","DOIUrl":"https://doi.org/10.14800/RCI.278","url":null,"abstract":"Certain cell signaling pharmaceutical targets have the potential to provide substantial clinical benefit when inhibited on some cell types yet elicit unwanted collateral damage when impeded on others. Thus, the appropriate therapeutic strategy for this situation would be to block preferentially receptor activation on the desired cell set. Taking advantage of the clustering within lipid rafts of toll-like receptor 4 (TLR4) and Fc gamma receptors (FcγR) during TLR4 activation, we have identified a mechanism that allows an antibody to block more favorably signaling on leukocytes, cells that underlie acute and chronic inflammatory processes. The anti-TLR4 monoclonal antibody (mAb), Hu 15C1, co-engages TLR4 and FcγRs to enhance its inhibitory potency via an avidity effect on FcγR-bearing cells. This novel mechanism of action allows the mAb to block efficiently TLR4 activation on FcγR-bearing inflammatory cells, while limiting the duration of effect on cells lacking FcγRs. As receptor clustering in lipid rafts is a common phenomenon, this mechanism could be exploited to anchor similar receptor-targeting mAbs or formats bearing an antibody Fc domain to desired cell types.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89372921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Gallo, S. Gatti, V. Sala, P. Comoglio, T. Crepaldi
Ischaemic heart disease is the main cause of death in western countries. Cardiac tissue is primarily damaged by cardiomyocyte cell death triggered by low oxygen supply to the heart (hypoxia). The current therapeutic approach is coronary angioplastic intervention or thrombolytic treatments to resume blood flow in the ischaemic heart. Unfortunately, reperfusion itself causes a burst of ROS production responsible for cardiomyocyte death and myocardial dysfunction. Indeed, the majority of patients surviving to acute myocardial infarction undergoes progressive heart failure, with 50% mortality at five years from diagnosis. Apoptosis of cardiomyocytes is dangerous both during ischaemia and reperfusion. In line with this concept, we have shown that treatment of H9c2 cardiomyoblasts with cobalt chloride (CoCl2), a chemical mimetic of hypoxia, induces caspase-dependent apoptosis. Unexpectedly, we found that 3-methyladenine, an inhibitor of autophagy initiation, partially prevents CoCl2-mediated cell death, indicating that also autophagy contributes to cardiomyoblast death. Consistently, we found an increase in the autophagic flux in dying cells. Mechanistically, we have shown that CoCl2 upregulates Redd1, Bnip3 and phospho-AMPK proteins and causes inhibition of mTOR, the main negative regulator of autophagy. In light of these observations, it is important to discover new therapeutic tools displaying a dual prosurvival mechanism. To this aim, we have analyzed the cardioprotective action of HGF/Met axis in hypoxic injury. To activate Met signaling we have used either the HGF ligand or two different monoclonal antibodies (mAbs) directed against the extracellular moiety of Met receptor. Owing a divalent structure, the two mAbs can dimerize and activate Met receptor, thus displaying agonist activity. Hypoxic injury was fully prevented by either HGF or Met agonist mAbs through both anti-apoptotic and anti-autophagic functions. By pharmacological inhibition we showed that activation of mTOR is the protective signaling downstream to Met, being involved in the anti-autophagic effect. In conclusion, HGF or Met agonist mAbs promote cell survival by negative dual regulation of apoptotic and autophagic cell death and represent promising new therapeutic tools to manage cardiac diseases.
{"title":"HGF/Met axis has anti-apoptotic and anti-autophagic function in hypoxic cardiac injury","authors":"S. Gallo, S. Gatti, V. Sala, P. Comoglio, T. Crepaldi","doi":"10.14800/RCI.234","DOIUrl":"https://doi.org/10.14800/RCI.234","url":null,"abstract":"Ischaemic heart disease is the main cause of death in western countries. Cardiac tissue is primarily damaged by cardiomyocyte cell death triggered by low oxygen supply to the heart (hypoxia). The current therapeutic approach is coronary angioplastic intervention or thrombolytic treatments to resume blood flow in the ischaemic heart. Unfortunately, reperfusion itself causes a burst of ROS production responsible for cardiomyocyte death and myocardial dysfunction. Indeed, the majority of patients surviving to acute myocardial infarction undergoes progressive heart failure, with 50% mortality at five years from diagnosis. Apoptosis of cardiomyocytes is dangerous both during ischaemia and reperfusion. In line with this concept, we have shown that treatment of H9c2 cardiomyoblasts with cobalt chloride (CoCl2), a chemical mimetic of hypoxia, induces caspase-dependent apoptosis. Unexpectedly, we found that 3-methyladenine, an inhibitor of autophagy initiation, partially prevents CoCl2-mediated cell death, indicating that also autophagy contributes to cardiomyoblast death. Consistently, we found an increase in the autophagic flux in dying cells. Mechanistically, we have shown that CoCl2 upregulates Redd1, Bnip3 and phospho-AMPK proteins and causes inhibition of mTOR, the main negative regulator of autophagy. In light of these observations, it is important to discover new therapeutic tools displaying a dual prosurvival mechanism. To this aim, we have analyzed the cardioprotective action of HGF/Met axis in hypoxic injury. To activate Met signaling we have used either the HGF ligand or two different monoclonal antibodies (mAbs) directed against the extracellular moiety of Met receptor. Owing a divalent structure, the two mAbs can dimerize and activate Met receptor, thus displaying agonist activity. Hypoxic injury was fully prevented by either HGF or Met agonist mAbs through both anti-apoptotic and anti-autophagic functions. By pharmacological inhibition we showed that activation of mTOR is the protective signaling downstream to Met, being involved in the anti-autophagic effect. In conclusion, HGF or Met agonist mAbs promote cell survival by negative dual regulation of apoptotic and autophagic cell death and represent promising new therapeutic tools to manage cardiac diseases.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74996292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
p75 neurotrophin receptor (p75 NTR ) regulates diverse functions, including survival, differentiation, growth, and apoptosis of neurons, through its association with a number of molecules. Accumulating evidence shows that β-amyloid precursor protein (APP)–related molecules, which also regulate multiple neuronal functions, interact with p75 NTR . APP is cleaved by secretases to generate several proteins including soluble β-amyloid precursor protein alpha (sAPPα), sAPPβ, and amyloid β (Aβ). Binding of Aβ to p75 NTR induces neuronal death. In contrast, sAPPα directly interacts with p75 NTR to enhance neurite outgrowth through the activation of protein kinase A (PKA). This review focuses on the molecular mechanisms and functions occurring as a consequence of interactions of p75 NTR with APP–related molecules.
{"title":"The functions and signaling pathways induced by the interactions of APP–related molecules with p75NTR","authors":"Y. Fujita, T. Yamashita","doi":"10.14800/RCI.283","DOIUrl":"https://doi.org/10.14800/RCI.283","url":null,"abstract":"p75 neurotrophin receptor (p75 NTR ) regulates diverse functions, including survival, differentiation, growth, and apoptosis of neurons, through its association with a number of molecules. Accumulating evidence shows that β-amyloid precursor protein (APP)–related molecules, which also regulate multiple neuronal functions, interact with p75 NTR . APP is cleaved by secretases to generate several proteins including soluble β-amyloid precursor protein alpha (sAPPα), sAPPβ, and amyloid β (Aβ). Binding of Aβ to p75 NTR induces neuronal death. In contrast, sAPPα directly interacts with p75 NTR to enhance neurite outgrowth through the activation of protein kinase A (PKA). This review focuses on the molecular mechanisms and functions occurring as a consequence of interactions of p75 NTR with APP–related molecules.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83273370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recently, cholinergic modulation of immune cells has drawn particular interests from researchers in clinical fields, which may lead to a breakthrough that produces a novel therapeutic modality. Other than the immunological aspects, cholinergic modulation may also provide clues for accelerating angiogenesis and preventing any associated muscle atrophy. In this Research highlight, we discuss our recent findings in the context of research advancements, focusing on nicotinic and non-nicotinic receptor-mediated anti-muscular atrophy effects.
{"title":"Nicotinic and non-nicotinic receptor-mediated mechanisms responsible for anti-atrophy effects in muscle","authors":"Y. Kakinuma","doi":"10.14800/RCI.286","DOIUrl":"https://doi.org/10.14800/RCI.286","url":null,"abstract":"Recently, cholinergic modulation of immune cells has drawn particular interests from researchers in clinical fields, which may lead to a breakthrough that produces a novel therapeutic modality. Other than the immunological aspects, cholinergic modulation may also provide clues for accelerating angiogenesis and preventing any associated muscle atrophy. In this Research highlight, we discuss our recent findings in the context of research advancements, focusing on nicotinic and non-nicotinic receptor-mediated anti-muscular atrophy effects.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85684330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Watanabe, M. Koizumi, J. Tatebe, T. Ikeda, T. Morita
The impact of chronic kidney disease (CKD) on the occurrence of cardiovascular disease (CVD) is a major concern and this reciprocal relation is currently so called "cardio-renal syndrome". More detailed understanding in its mechanism may have a possibility to reduce the global burden of CVD. Of note, uremic toxins have been known to accumulate in the progression of CKD and play an important role for worsening renal function, on the other hand, recent studies suggest that they also negatively affect cardiovascular system. In this review, we delve into the role of aryl hydrocarbon receptor (AhR) in uremic toxicities, as highlighted in our latest work and give a new insight for the mechanism of cardio-renal syndrome.
{"title":"Vascular Senescence in Chronic kidney Disease; Association of Aryl Hydrocarbon Receptor Activated by Indoxyl Sulfate","authors":"I. Watanabe, M. Koizumi, J. Tatebe, T. Ikeda, T. Morita","doi":"10.14800/RCI.212","DOIUrl":"https://doi.org/10.14800/RCI.212","url":null,"abstract":"The impact of chronic kidney disease (CKD) on the occurrence of cardiovascular disease (CVD) is a major concern and this reciprocal relation is currently so called \"cardio-renal syndrome\". More detailed understanding in its mechanism may have a possibility to reduce the global burden of CVD. Of note, uremic toxins have been known to accumulate in the progression of CKD and play an important role for worsening renal function, on the other hand, recent studies suggest that they also negatively affect cardiovascular system. In this review, we delve into the role of aryl hydrocarbon receptor (AhR) in uremic toxicities, as highlighted in our latest work and give a new insight for the mechanism of cardio-renal syndrome.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"144 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87368761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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