The Experts below are selected from a list of 3117 Experts worldwide ranked by ideXlab platform
Guangdong Yang - One of the best experts on this subject based on the ideXlab platform.
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Cystathionine gamma lyase h2s system suppresses hepatic acetyl coa accumulation and nonalcoholic fatty liver disease in mice
Life Sciences, 2020Co-Authors: Amr Ali, Yanjie Zhang, Rui Wang, Yanxi Pei, Guangdong YangAbstract:Abstract Aims Hydrogen sulfide (H2S) as a novel gasotransmitter can be endogenously produced in liver by Cystathionine Gamma-Lyase (CSE). The dysfunctions of CSE/H2S system have been linked to various liver diseases. Acetyl-CoA is the key intermediate from the metabolism of lipid. This study examined the roles of H2S in hepatic acetyl-CoA and lipid metabolism. Materials and methods Both in vitro cell model and in vivo animal model of lipid accumulation were used in this study. Western blotting and real-time PCR were used for analysis of protein and mRNA expression. Acetyl-CoA was analyzed by a coupled enzyme assay, and lipid accumulation was observed with Oil Red O staining. Key findings Incubation of human liver carcinoma (HepG2) cells with a mixture of free fatty acids (FFAs) or high glucose reduced CSE expression and H2S production, promoted intracellular accumulation of acetyl-CoA and lipid. Supply of exogenous NaHS or cysteine reduced acetyl-CoA contents and lipid accumulation, while blockage of CSE activity promoted intracellular lipid accumulation. Furthermore, H2S blocked FFAs-induced transcriptions of de novo lipogenesis, inflammation, and fibrosis-related genes. In vivo, knockout of CSE gene stimulated more hepatic acetyl-CoA and lipid accumulation in mice induced by high-fat choline-deficient diet. The expressions of lipogenesis, inflammation, and fibrosis-related genes were significantly higher in liver tissues from CSE knockout mice when compared with wild-type mice. Significance CSE/H2S system is indispensable for maintaining the homeostasis of acetyl-CoA and lipid accumulation and protecting from the development of inflammation and fibrosis in liver under excessive caloric ingestion.
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Cystathionine Gamma-Lyase/H2S system suppresses hepatic acetyl-CoA accumulation and nonalcoholic fatty liver disease in mice.
Life sciences, 2020Co-Authors: Amr Ali, Yanjie Zhang, Rui Wang, Yanxi Pei, Guangdong YangAbstract:Abstract Aims Hydrogen sulfide (H2S) as a novel gasotransmitter can be endogenously produced in liver by Cystathionine Gamma-Lyase (CSE). The dysfunctions of CSE/H2S system have been linked to various liver diseases. Acetyl-CoA is the key intermediate from the metabolism of lipid. This study examined the roles of H2S in hepatic acetyl-CoA and lipid metabolism. Materials and methods Both in vitro cell model and in vivo animal model of lipid accumulation were used in this study. Western blotting and real-time PCR were used for analysis of protein and mRNA expression. Acetyl-CoA was analyzed by a coupled enzyme assay, and lipid accumulation was observed with Oil Red O staining. Key findings Incubation of human liver carcinoma (HepG2) cells with a mixture of free fatty acids (FFAs) or high glucose reduced CSE expression and H2S production, promoted intracellular accumulation of acetyl-CoA and lipid. Supply of exogenous NaHS or cysteine reduced acetyl-CoA contents and lipid accumulation, while blockage of CSE activity promoted intracellular lipid accumulation. Furthermore, H2S blocked FFAs-induced transcriptions of de novo lipogenesis, inflammation, and fibrosis-related genes. In vivo, knockout of CSE gene stimulated more hepatic acetyl-CoA and lipid accumulation in mice induced by high-fat choline-deficient diet. The expressions of lipogenesis, inflammation, and fibrosis-related genes were significantly higher in liver tissues from CSE knockout mice when compared with wild-type mice. Significance CSE/H2S system is indispensable for maintaining the homeostasis of acetyl-CoA and lipid accumulation and protecting from the development of inflammation and fibrosis in liver under excessive caloric ingestion.
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Golgi Stress Response, Hydrogen Sulfide Metabolism, and Intracellular Calcium Homeostasis.
Antioxidants & redox signaling, 2020Co-Authors: Yanjie Zhang, Rui Wang, Yanxi Pei, Yuehong Wang, Ethan Read, Guangdong YangAbstract:Aims: The physiological and pathological importance of hydrogen sulfide (H2S) as a novel gasotransmitter has been widely recognized. Cystathionine Gamma-Lyase (CSE) is one of the major H2S-producin...
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Induction of Cystathionine Gamma-Lyase expression and metallothionein-1 S-sulfhydration alleviate cadmium-induced cell death in myoblast cells.
Ecotoxicology and environmental safety, 2019Co-Authors: Yanjie Zhang, Yanxi Pei, Amr Ali, Zhuping Jin, Guangdong YangAbstract:Hydrogen sulfide (H2S), a multifunctional gasotransmitter, participates in a wide range of cellular signal transduction and pathophysiological processes. Cystathionine Gamma-Lyase (CSE) acts as a major H2S-generating enzyme in peripheral organs and tissues. As a cysteine-rich and heavy metal-binding protein, metallothionein-1 (MT-1) is known to protect cells from various environmental stresses. Here we demonstrated that exposure of cadmium (Cd) induced oxidative stress, depleted intracellular thiols, and stimulated apoptotic cell death in mouse myoblast cells. CSE expression and H2S production were significantly enhanced by Cd treatment. NaHS, a well-known H2S donor, at physiologically relevant concentration significantly alleviated Cd-induced damage in both myoblasts and mouse skeletal muscles. In contrast, down-regulation of CSE/H2S system deteriorated Cd-stimulated oxidative stress and cell death. Exposure of the cells to Cd lead to increased expressions of metal regulatory transcription factor 1 and MT-1, while siRNA-mediated MT-1 knockdown alleviated Cd-induced CSE expression and caused more oxidative stress and cell death. In addition, H2S post-translationally modified MT-1 by S-sulfhydration and stabilized zinc-protein complex. Taken together, these data suggest that CSE/H2S system would protect myoblasts and skeletal muscles from Cd-induced damage by S-sufhydrating MT-1.
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Cystathionine gamma lyase hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice
Biochimica et Biophysica Acta, 2018Co-Authors: Guangdong Yang, Yanjie Zhang, Yanxi Pei, Mélanie Racine, Simran Baath, Thomas J. S. Merritt, Rui WangAbstract:Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter analogous to nitric oxide and carbon monoxide. Cystathionine Gamma-Lyase (CSE)-derived H2S is implicated in the regulation of insulin resistance and glucose metabolism, but the involvement of CSE/H2S system in energy homeostasis and fat mass has not been extensively explored. In this study, a potential functional role of the CSE/H2S system in in vitro adipocyte differentiation and in vivo adipogenesis and the underlying mechanism was investigated. CSE expression and H2S production were increased during adipocyte differentiation, and that the pattern of CSE mRNA expression was similar to that of CCAAT/enhancer-binding protein (C/EBP) β and δ, two key regulators for adipogenesis. C/EBPβ and γ bind to the CCAAT box in CSE promoter and stimulate CSE gene transcription. H2S induced PPARγ transactivation activity by S-sulfhydrating all the cysteine residues in the DNA binding domain and stimulated adipogenesis. High fat diet-induced fat mass was lost in CSE deficient mice, and exogenously applied H2S promoted fat mass accumulation in fruit flies. In conclusion, CSE/H2S system is essential for adipogenesis and fat mass accumulation through enhancement of PPARγ function in adipocytes. This study suggests that the CSE/H2S system is involved in the pathogenesis of obesity in mice.
Rui Wang - One of the best experts on this subject based on the ideXlab platform.
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Cystathionine gamma lyase h2s system suppresses hepatic acetyl coa accumulation and nonalcoholic fatty liver disease in mice
Life Sciences, 2020Co-Authors: Amr Ali, Yanjie Zhang, Rui Wang, Yanxi Pei, Guangdong YangAbstract:Abstract Aims Hydrogen sulfide (H2S) as a novel gasotransmitter can be endogenously produced in liver by Cystathionine Gamma-Lyase (CSE). The dysfunctions of CSE/H2S system have been linked to various liver diseases. Acetyl-CoA is the key intermediate from the metabolism of lipid. This study examined the roles of H2S in hepatic acetyl-CoA and lipid metabolism. Materials and methods Both in vitro cell model and in vivo animal model of lipid accumulation were used in this study. Western blotting and real-time PCR were used for analysis of protein and mRNA expression. Acetyl-CoA was analyzed by a coupled enzyme assay, and lipid accumulation was observed with Oil Red O staining. Key findings Incubation of human liver carcinoma (HepG2) cells with a mixture of free fatty acids (FFAs) or high glucose reduced CSE expression and H2S production, promoted intracellular accumulation of acetyl-CoA and lipid. Supply of exogenous NaHS or cysteine reduced acetyl-CoA contents and lipid accumulation, while blockage of CSE activity promoted intracellular lipid accumulation. Furthermore, H2S blocked FFAs-induced transcriptions of de novo lipogenesis, inflammation, and fibrosis-related genes. In vivo, knockout of CSE gene stimulated more hepatic acetyl-CoA and lipid accumulation in mice induced by high-fat choline-deficient diet. The expressions of lipogenesis, inflammation, and fibrosis-related genes were significantly higher in liver tissues from CSE knockout mice when compared with wild-type mice. Significance CSE/H2S system is indispensable for maintaining the homeostasis of acetyl-CoA and lipid accumulation and protecting from the development of inflammation and fibrosis in liver under excessive caloric ingestion.
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Cystathionine Gamma-Lyase/H2S system suppresses hepatic acetyl-CoA accumulation and nonalcoholic fatty liver disease in mice.
Life sciences, 2020Co-Authors: Amr Ali, Yanjie Zhang, Rui Wang, Yanxi Pei, Guangdong YangAbstract:Abstract Aims Hydrogen sulfide (H2S) as a novel gasotransmitter can be endogenously produced in liver by Cystathionine Gamma-Lyase (CSE). The dysfunctions of CSE/H2S system have been linked to various liver diseases. Acetyl-CoA is the key intermediate from the metabolism of lipid. This study examined the roles of H2S in hepatic acetyl-CoA and lipid metabolism. Materials and methods Both in vitro cell model and in vivo animal model of lipid accumulation were used in this study. Western blotting and real-time PCR were used for analysis of protein and mRNA expression. Acetyl-CoA was analyzed by a coupled enzyme assay, and lipid accumulation was observed with Oil Red O staining. Key findings Incubation of human liver carcinoma (HepG2) cells with a mixture of free fatty acids (FFAs) or high glucose reduced CSE expression and H2S production, promoted intracellular accumulation of acetyl-CoA and lipid. Supply of exogenous NaHS or cysteine reduced acetyl-CoA contents and lipid accumulation, while blockage of CSE activity promoted intracellular lipid accumulation. Furthermore, H2S blocked FFAs-induced transcriptions of de novo lipogenesis, inflammation, and fibrosis-related genes. In vivo, knockout of CSE gene stimulated more hepatic acetyl-CoA and lipid accumulation in mice induced by high-fat choline-deficient diet. The expressions of lipogenesis, inflammation, and fibrosis-related genes were significantly higher in liver tissues from CSE knockout mice when compared with wild-type mice. Significance CSE/H2S system is indispensable for maintaining the homeostasis of acetyl-CoA and lipid accumulation and protecting from the development of inflammation and fibrosis in liver under excessive caloric ingestion.
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Golgi Stress Response, Hydrogen Sulfide Metabolism, and Intracellular Calcium Homeostasis.
Antioxidants & redox signaling, 2020Co-Authors: Yanjie Zhang, Rui Wang, Yanxi Pei, Yuehong Wang, Ethan Read, Guangdong YangAbstract:Aims: The physiological and pathological importance of hydrogen sulfide (H2S) as a novel gasotransmitter has been widely recognized. Cystathionine Gamma-Lyase (CSE) is one of the major H2S-producin...
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Cystathionine gamma lyase hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice
Biochimica et Biophysica Acta, 2018Co-Authors: Guangdong Yang, Yanjie Zhang, Yanxi Pei, Mélanie Racine, Simran Baath, Thomas J. S. Merritt, Rui WangAbstract:Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter analogous to nitric oxide and carbon monoxide. Cystathionine Gamma-Lyase (CSE)-derived H2S is implicated in the regulation of insulin resistance and glucose metabolism, but the involvement of CSE/H2S system in energy homeostasis and fat mass has not been extensively explored. In this study, a potential functional role of the CSE/H2S system in in vitro adipocyte differentiation and in vivo adipogenesis and the underlying mechanism was investigated. CSE expression and H2S production were increased during adipocyte differentiation, and that the pattern of CSE mRNA expression was similar to that of CCAAT/enhancer-binding protein (C/EBP) β and δ, two key regulators for adipogenesis. C/EBPβ and γ bind to the CCAAT box in CSE promoter and stimulate CSE gene transcription. H2S induced PPARγ transactivation activity by S-sulfhydrating all the cysteine residues in the DNA binding domain and stimulated adipogenesis. High fat diet-induced fat mass was lost in CSE deficient mice, and exogenously applied H2S promoted fat mass accumulation in fruit flies. In conclusion, CSE/H2S system is essential for adipogenesis and fat mass accumulation through enhancement of PPARγ function in adipocytes. This study suggests that the CSE/H2S system is involved in the pathogenesis of obesity in mice.
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Cystathionine Gamma-Lyase/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice.
Biochimica et biophysica acta. Molecular and cell biology of lipids, 2017Co-Authors: Guangdong Yang, Yanjie Zhang, Yanxi Pei, Mélanie Racine, Simran Baath, Thomas J. S. Merritt, Rui WangAbstract:Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter analogous to nitric oxide and carbon monoxide. Cystathionine Gamma-Lyase (CSE)-derived H2S is implicated in the regulation of insulin resistance and glucose metabolism, but the involvement of CSE/H2S system in energy homeostasis and fat mass has not been extensively explored. In this study, a potential functional role of the CSE/H2S system in in vitro adipocyte differentiation and in vivo adipogenesis and the underlying mechanism was investigated. CSE expression and H2S production were increased during adipocyte differentiation, and that the pattern of CSE mRNA expression was similar to that of CCAAT/enhancer-binding protein (C/EBP) β and δ, two key regulators for adipogenesis. C/EBPβ and γ bind to the CCAAT box in CSE promoter and stimulate CSE gene transcription. H2S induced PPARγ transactivation activity by S-sulfhydrating all the cysteine residues in the DNA binding domain and stimulated adipogenesis. High fat diet-induced fat mass was lost in CSE deficient mice, and exogenously applied H2S promoted fat mass accumulation in fruit flies. In conclusion, CSE/H2S system is essential for adipogenesis and fat mass accumulation through enhancement of PPARγ function in adipocytes. This study suggests that the CSE/H2S system is involved in the pathogenesis of obesity in mice.
Xin Zhong - One of the best experts on this subject based on the ideXlab platform.
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calcium sensing receptor initiating Cystathionine gamma lyase hydrogen sulfide pathway to inhibit platelet activation in hyperhomocysteinemia rat
Experimental Cell Research, 2017Co-Authors: Yuwen Wang, Weihua Zhang, Ziqing Zhao, Fei Gao, Shiyun Dong, Yanhong Liu, Sa Shi, Xin ZhongAbstract:Abstract Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H 2 S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H 2 S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous Cystathionine-Gamma-Lyase (CSE, a major enzyme that produces H 2 S)/H 2 S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured. The aggregation rate and expression of P-selectin of platelets were assessed. Additionally, the expression levels of CaSR and CSE in the aorta of rats were examined by western blotting. The mitochondrial membrane potential and the production of reactive oxygen species (ROS) were measured; the expression of phospho-calmodulin kinases II (p-CaMK II) and Von Willebrand Factor (vWF) of cultured ECs from rat thoracic aortas were measured. We found that the aggregation rate and the expression of P-selectin of platelets increased, and the expression of CaSR and CSE decreased in HHcy rats. In the ECs of HHcy group, the ROS production increased and the mitochondrial membrane potential decreased markedly, the expression of CSE and the p-CaMK II increased after treatment with CaSR agonist while decreased upon administration of U73122 (PLC-specific inhibitor) and 2-APB (IP 3 Receptor inhibitor). CaSR agonist or NaHS significantly reversed the ECs injured and platelet aggregation caused by hyperhomocysteinemia. Our results demonstrate that CaSR regulates the endogenous CSE/H 2 S pathway to inhibit the activation of platelets which concerts the protection of ECs in hyperhomocysteinemia.
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Calcium sensing receptor initiating Cystathionine-Gamma-Lyase/hydrogen sulfide pathway to inhibit platelet activation in hyperhomocysteinemia rat
Experimental cell research, 2017Co-Authors: Yuwen Wang, Weihua Zhang, Ziqing Zhao, Shi, Fei Gao, Shiyun Dong, Yanhong Liu, Xin ZhongAbstract:Abstract Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H 2 S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H 2 S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous Cystathionine-Gamma-Lyase (CSE, a major enzyme that produces H 2 S)/H 2 S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured. The aggregation rate and expression of P-selectin of platelets were assessed. Additionally, the expression levels of CaSR and CSE in the aorta of rats were examined by western blotting. The mitochondrial membrane potential and the production of reactive oxygen species (ROS) were measured; the expression of phospho-calmodulin kinases II (p-CaMK II) and Von Willebrand Factor (vWF) of cultured ECs from rat thoracic aortas were measured. We found that the aggregation rate and the expression of P-selectin of platelets increased, and the expression of CaSR and CSE decreased in HHcy rats. In the ECs of HHcy group, the ROS production increased and the mitochondrial membrane potential decreased markedly, the expression of CSE and the p-CaMK II increased after treatment with CaSR agonist while decreased upon administration of U73122 (PLC-specific inhibitor) and 2-APB (IP 3 Receptor inhibitor). CaSR agonist or NaHS significantly reversed the ECs injured and platelet aggregation caused by hyperhomocysteinemia. Our results demonstrate that CaSR regulates the endogenous CSE/H 2 S pathway to inhibit the activation of platelets which concerts the protection of ECs in hyperhomocysteinemia.
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Calcium sensing receptor regulating smooth muscle cells proliferation through initiating Cystathionine-Gamma-Lyase/hydrogen sulfide pathway in diabetic rat.
Cellular physiology and biochemistry : international journal of experimental cellular physiology biochemistry and pharmacology, 2015Co-Authors: Xin Zhong, Yuwen Wang, Shiyun Dong, Aili Sun, Fan Yang, Dan Zheng, Yajun Zhao, Guangdong YangAbstract:Aims: Hydrogen sulfide (H2S) inhibits the proliferation of vascular smooth muscle cells (VSMCs). However, how Cystathionine-Gamma-Lyase (CSE), a major enzyme that produces H2S, is regulated remains unknown. Whether calcium-sensing receptor (CaSR) inhibits the proliferation of VSMCs by regulating the endogenous CSE/H2S pathway in diabetic rat has not been previously investigated. Methods and Results: The morphological and ultrastructure alterations were tested by transmission electron microscopy, changes in the H2S concentration and the relaxation of the mesenteric secondary artery loop of diabetic rats were determined by Multiskan spectrum microplate spectrophotometer and isometric force transducer. Additionally, the expression levels of CaSR, CSE and Cyclin D1 in the mesenteric arteries of rats were examined by western blotting. The intracellular calcium concentration, the expression of p-CaMK II (phospho-calmodulin kinases II), CSE activity, the concentration of endogenous H2S and the proliferation of cultured VSMCs from rat thoracic aortas were measured by using confocal microscope, western blotting, microplate spectrophotometer, MTT and BrdU, respectively. The VSMC layer thickened, the H2S concentration dropped, the relaxation of the mesenteric secondary artery rings weakened, and the expression of CaSR and CSE decreased whereas the expression of Cyclin D1 increased in diabetic rats compared with the control group. The [Ca2+]i of VSMCs increased upon treatment with CaSR agonists (10 µM Calindol and 2.5 mM CaCl2), while it decreased upon administration of calhex231, U73122 and 2-APB. The expression of p-CaMK II and CSE increased upon treatment with CaSR agonists in VSMCs. CSE activity and the endogenous H2S concentration decreased in response to high glucose, while it increased with treatment of CaSR agonists. The proliferation rate increased in response to high glucose, and CaSR agonists or NaHS significantly reversed the proliferation of VSMCs caused by high glucose. Conclusions: Our results demonstrated that CaSR regulated the endogenous CSE/H2S pathway to inhibit the proliferation of VSMCs in both diabetic and high glucose models.
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calcium sensing receptor regulating smooth muscle cells proliferation through initiating Cystathionine gamma lyase hydrogen sulfide pathway in diabetic rat
Cellular Physiology and Biochemistry, 2015Co-Authors: Xin Zhong, Guangdong Yang, Yuwen Wang, Shiyun Dong, Aili Sun, Fan Yang, Dan Zheng, Yajun Zhao, Dianjun Sun, Weihua ZhangAbstract:Aims: Hydrogen sulfide (H2S) inhibits the proliferation of vascular smooth muscle cells (VSMCs). However, how Cystathionine-Gamma-Lyase (CSE), a major enzyme that produces H2S, is regulated remains unknown. Whether calcium-sensing receptor (CaSR) inhibits the proliferation of VSMCs by regulating the endogenous CSE/H2S pathway in diabetic rat has not been previously investigated. Methods and Results: The morphological and ultrastructure alterations were tested by transmission electron microscopy, changes in the H2S concentration and the relaxation of the mesenteric secondary artery loop of diabetic rats were determined by Multiskan spectrum microplate spectrophotometer and isometric force transducer. Additionally, the expression levels of CaSR, CSE and Cyclin D1 in the mesenteric arteries of rats were examined by western blotting. The intracellular calcium concentration, the expression of p-CaMK II (phospho-calmodulin kinases II), CSE activity, the concentration of endogenous H2S and the proliferation of cultured VSMCs from rat thoracic aortas were measured by using confocal microscope, western blotting, microplate spectrophotometer, MTT and BrdU, respectively. The VSMC layer thickened, the H2S concentration dropped, the relaxation of the mesenteric secondary artery rings weakened, and the expression of CaSR and CSE decreased whereas the expression of Cyclin D1 increased in diabetic rats compared with the control group. The [Ca2+]i of VSMCs increased upon treatment with CaSR agonists (10 µM Calindol and 2.5 mM CaCl2), while it decreased upon administration of calhex231, U73122 and 2-APB. The expression of p-CaMK II and CSE increased upon treatment with CaSR agonists in VSMCs. CSE activity and the endogenous H2S concentration decreased in response to high glucose, while it increased with treatment of CaSR agonists. The proliferation rate increased in response to high glucose, and CaSR agonists or NaHS significantly reversed the proliferation of VSMCs caused by high glucose. Conclusions: Our results demonstrated that CaSR regulated the endogenous CSE/H2S pathway to inhibit the proliferation of VSMCs in both diabetic and high glucose models.
Weihua Zhang - One of the best experts on this subject based on the ideXlab platform.
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calcium sensing receptor initiating Cystathionine gamma lyase hydrogen sulfide pathway to inhibit platelet activation in hyperhomocysteinemia rat
Experimental Cell Research, 2017Co-Authors: Yuwen Wang, Weihua Zhang, Ziqing Zhao, Fei Gao, Shiyun Dong, Yanhong Liu, Sa Shi, Xin ZhongAbstract:Abstract Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H 2 S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H 2 S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous Cystathionine-Gamma-Lyase (CSE, a major enzyme that produces H 2 S)/H 2 S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured. The aggregation rate and expression of P-selectin of platelets were assessed. Additionally, the expression levels of CaSR and CSE in the aorta of rats were examined by western blotting. The mitochondrial membrane potential and the production of reactive oxygen species (ROS) were measured; the expression of phospho-calmodulin kinases II (p-CaMK II) and Von Willebrand Factor (vWF) of cultured ECs from rat thoracic aortas were measured. We found that the aggregation rate and the expression of P-selectin of platelets increased, and the expression of CaSR and CSE decreased in HHcy rats. In the ECs of HHcy group, the ROS production increased and the mitochondrial membrane potential decreased markedly, the expression of CSE and the p-CaMK II increased after treatment with CaSR agonist while decreased upon administration of U73122 (PLC-specific inhibitor) and 2-APB (IP 3 Receptor inhibitor). CaSR agonist or NaHS significantly reversed the ECs injured and platelet aggregation caused by hyperhomocysteinemia. Our results demonstrate that CaSR regulates the endogenous CSE/H 2 S pathway to inhibit the activation of platelets which concerts the protection of ECs in hyperhomocysteinemia.
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Calcium sensing receptor initiating Cystathionine-Gamma-Lyase/hydrogen sulfide pathway to inhibit platelet activation in hyperhomocysteinemia rat
Experimental cell research, 2017Co-Authors: Yuwen Wang, Weihua Zhang, Ziqing Zhao, Shi, Fei Gao, Shiyun Dong, Yanhong Liu, Xin ZhongAbstract:Abstract Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H 2 S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H 2 S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous Cystathionine-Gamma-Lyase (CSE, a major enzyme that produces H 2 S)/H 2 S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured. The aggregation rate and expression of P-selectin of platelets were assessed. Additionally, the expression levels of CaSR and CSE in the aorta of rats were examined by western blotting. The mitochondrial membrane potential and the production of reactive oxygen species (ROS) were measured; the expression of phospho-calmodulin kinases II (p-CaMK II) and Von Willebrand Factor (vWF) of cultured ECs from rat thoracic aortas were measured. We found that the aggregation rate and the expression of P-selectin of platelets increased, and the expression of CaSR and CSE decreased in HHcy rats. In the ECs of HHcy group, the ROS production increased and the mitochondrial membrane potential decreased markedly, the expression of CSE and the p-CaMK II increased after treatment with CaSR agonist while decreased upon administration of U73122 (PLC-specific inhibitor) and 2-APB (IP 3 Receptor inhibitor). CaSR agonist or NaHS significantly reversed the ECs injured and platelet aggregation caused by hyperhomocysteinemia. Our results demonstrate that CaSR regulates the endogenous CSE/H 2 S pathway to inhibit the activation of platelets which concerts the protection of ECs in hyperhomocysteinemia.
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calcium sensing receptor regulating smooth muscle cells proliferation through initiating Cystathionine gamma lyase hydrogen sulfide pathway in diabetic rat
Cellular Physiology and Biochemistry, 2015Co-Authors: Xin Zhong, Guangdong Yang, Yuwen Wang, Shiyun Dong, Aili Sun, Fan Yang, Dan Zheng, Yajun Zhao, Dianjun Sun, Weihua ZhangAbstract:Aims: Hydrogen sulfide (H2S) inhibits the proliferation of vascular smooth muscle cells (VSMCs). However, how Cystathionine-Gamma-Lyase (CSE), a major enzyme that produces H2S, is regulated remains unknown. Whether calcium-sensing receptor (CaSR) inhibits the proliferation of VSMCs by regulating the endogenous CSE/H2S pathway in diabetic rat has not been previously investigated. Methods and Results: The morphological and ultrastructure alterations were tested by transmission electron microscopy, changes in the H2S concentration and the relaxation of the mesenteric secondary artery loop of diabetic rats were determined by Multiskan spectrum microplate spectrophotometer and isometric force transducer. Additionally, the expression levels of CaSR, CSE and Cyclin D1 in the mesenteric arteries of rats were examined by western blotting. The intracellular calcium concentration, the expression of p-CaMK II (phospho-calmodulin kinases II), CSE activity, the concentration of endogenous H2S and the proliferation of cultured VSMCs from rat thoracic aortas were measured by using confocal microscope, western blotting, microplate spectrophotometer, MTT and BrdU, respectively. The VSMC layer thickened, the H2S concentration dropped, the relaxation of the mesenteric secondary artery rings weakened, and the expression of CaSR and CSE decreased whereas the expression of Cyclin D1 increased in diabetic rats compared with the control group. The [Ca2+]i of VSMCs increased upon treatment with CaSR agonists (10 µM Calindol and 2.5 mM CaCl2), while it decreased upon administration of calhex231, U73122 and 2-APB. The expression of p-CaMK II and CSE increased upon treatment with CaSR agonists in VSMCs. CSE activity and the endogenous H2S concentration decreased in response to high glucose, while it increased with treatment of CaSR agonists. The proliferation rate increased in response to high glucose, and CaSR agonists or NaHS significantly reversed the proliferation of VSMCs caused by high glucose. Conclusions: Our results demonstrated that CaSR regulated the endogenous CSE/H2S pathway to inhibit the proliferation of VSMCs in both diabetic and high glucose models.
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Is Cystathionine Gamma-Lyase protein expressed in the heart?
Biochemical and biophysical research communications, 2012Co-Authors: Weihua Zhang, Guangdong Yang, Rui WangAbstract:Abstract Hydrogen sulfide (H2S) has emerged as an important gasotransmitter, offering protection against ischemia–reperfusion damage to the heart. Cystathionine Gamma-Lyase (CSE) is believed to be the major H2S-generating enzyme in the heart. Quite contrary to the general contemplation, CSE protein in cardiac tissues has not been convincingly detected and it has become an issue of controversy. In the present study, we isolated cardiac tissues from wild type (WT) and CSE knockout mice or the rat. CSE expression at transcriptional and translational levels were assayed by RT-PCR and Western Blotting with five different antibodies (four commercial products and one homemade), respectively. Cardiac H2S production rate was also examined. Our data validated the expression of CSE mRNA in the heart of WT mice or rats, not in CSE KO mice. Using all 5 different anti-CSE antibodies, we could not detect CSE proteins in mouse or rat cardiac tissues or in cultured rat cardiomyocytes. On the other hand, CSE protein was detectable in liver tissues from WT mice with the expected molecular mass of 43.6 kDa. H2S production rate of heart tissues in CSE KO mice was significantly decreased compared with that in WT mice. In the presence of an CSE inhibitor, d , l -propargylglycine, H2S production rate of heart tissues from WT mice was inhibited by approximately 80%. It appears that CSE mediates mostly endogenous H2S production in heart tissues. However, the available anti-CSE antibodies could not detect CSE proteins in rat and mouse heart tissues or rat cardiomyocytes.
Robert T Kinobe - One of the best experts on this subject based on the ideXlab platform.
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inhibition of Cystathionine gamma lyase and the biosynthesis of endogenous hydrogen sulphide ameliorates gentamicin induced nephrotoxicity
European Journal of Pharmacology, 2012Co-Authors: Van P Dam, Jennifer L Scott, Anthony Ross, Robert T KinobeAbstract:Clinical use of gentamicin over prolonged periods is limited because of dose- and time-dependent nephrotoxicity. Primarily, lysosomal phospholipidosis, intracellular oxidative stress and heightened inflammation have been implicated. Hydrogen sulphide is an endogenously produced signal transduction molecule with strong anti-inflammatory, anti-apoptotic and cytoprotective properties. In several models of inflammatory disease however, tissue damage has been associated with increased activity of Cystathionine Gamma-Lyase, biosynthesis of hydrogen sulphide and activation of leukocytes. The aim of this study was to determine effects of inhibiting hydrogen sulphide biosynthesis by DL-propargyl glycine (an irreversible inhibitor of Cystathionine Gamma-Lyase) on inflammation, necrosis and renal function, following treatment with gentamicin in rats. Adult female Sprague–Dawley rats were divided into six groups and treated with; physiological saline, sodium hydrosulphide, DL-propargyl glycine, gentamicin, a combination of gentamicin and sodium hydrosulphide, or gentamicin and DL-propargyl glycine respectively. Gentamicin-induced histopathological changes including inflammatory cell infiltration and tubular necrosis were attenuated by co-administering gentamicin with DL-propargyl glycine (P < 0.05 compared to saline controls and P < 0.05 compared to gentamicin only). Similarly, DL-propargyl glycine caused a significant reduction (P < 0.05) in lipid peroxidation, production of superoxide and the activation of tumour necrosis factor-alpha in gentamicin-treated animals. These data show that protective effects of DL-propargyl glycine might be related at least in part, to the reduced inflammatory responses observed in animals treated with both gentamicin and DL-propargyl glycine. Thus, enzyme systems involved in hydrogen sulphide biosynthesis may offer a viable therapeutic target in alleviating the nephrotoxic effects of gentamicin.
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Inhibition of Cystathionine Gamma-Lyase and the biosynthesis of endogenous hydrogen sulphide ameliorates gentamicin-induced nephrotoxicity.
European journal of pharmacology, 2012Co-Authors: Van P Dam, Jennifer L Scott, Anthony Ross, Robert T KinobeAbstract:Clinical use of gentamicin over prolonged periods is limited because of dose- and time-dependent nephrotoxicity. Primarily, lysosomal phospholipidosis, intracellular oxidative stress and heightened inflammation have been implicated. Hydrogen sulphide is an endogenously produced signal transduction molecule with strong anti-inflammatory, anti-apoptotic and cytoprotective properties. In several models of inflammatory disease however, tissue damage has been associated with increased activity of Cystathionine Gamma-Lyase, biosynthesis of hydrogen sulphide and activation of leukocytes. The aim of this study was to determine effects of inhibiting hydrogen sulphide biosynthesis by DL-propargyl glycine (an irreversible inhibitor of Cystathionine Gamma-Lyase) on inflammation, necrosis and renal function, following treatment with gentamicin in rats. Adult female Sprague-Dawley rats were divided into six groups and treated with; physiological saline, sodium hydrosulphide, DL-propargyl glycine, gentamicin, a combination of gentamicin and sodium hydrosulphide, or gentamicin and DL-propargyl glycine respectively. Gentamicin-induced histopathological changes including inflammatory cell infiltration and tubular necrosis were attenuated by co-administering gentamicin with DL-propargyl glycine (P
