Background The classic glycine receptor （GlyR） in the central nervous system is a ligand-gated membrane-spanning ion channel. Recent studies have provided evidence for the existence of GlyR in endothelial cells, ren...Background The classic glycine receptor （GlyR） in the central nervous system is a ligand-gated membrane-spanning ion channel. Recent studies have provided evidence for the existence of GlyR in endothelial cells, renal proximal tubular cells and most leukocytes. In contrast, no evidence for GlyR in myocardial cells has been found so far. Our recent researches have showed that glycine could protect myocardial cells from the damage induced by lipopolysaccharide （LPS）. Further studies suggest that myocardial cells could contain GlyR or binding site of glycine. Methods In isolated rat heart damaged by LPS, the myocardial monophasic action potential （MAP）, the heart rate （HR） the myocardial tension and the activities of lactate dehydrogenase （LDH） from the coronary effluent were determined. The concentration of intracellular free calcium （[Ca^2＋]i） was measured in cardiomyocytes injured by LPS and by hypoxia/reoxygenation （H/R）, which excludes the possibility that reduced calcium influx because of LPS neutralized by glycine. Immunohistochemistry was used to detect the GlyR in myocardial tissue. GlyR and its subunit in the purified cultured cardiomyocytes were identified by Western blotting. Results Although significant improvement in the MAP/MAPD20, HR, and reduction in LDH release were observed in glycine ＋ LPS hearts, myocardial tension did not recover. Further studies demonstrated that glycine could prevent rat mycordial cells from LPS and hypoxia/reoxygenation injury （no endotoxin） by attenuating calcium influx. Immunohistochemistry exhibited a positive green-fluorescence signaling along the cardiac muscle fibers. Western blotting shows that the purified cultured cardiomyocytes express GlyR β subunit, but GlyR α1 subunit could not be detected. Conclusions The results suggest that glycine receptor is expressed in cardiomyocytes and participates in cytoprotection from LPS and hypoxia/reoxygenation injury. Glycine could directly activate GlyR on the cardiomyocytes and prevent calcium influx into the cardiomyocytes.展开更多
Glycine is a well-documented cytoprotective agent.However,whether it has a protective effect against myocar-dial ischemia-reperfusion injury in vivo is still unknown.By using an open-chest anesthetized rat model,we fo...Glycine is a well-documented cytoprotective agent.However,whether it has a protective effect against myocar-dial ischemia-reperfusion injury in vivo is still unknown.By using an open-chest anesthetized rat model,we found that glycine reduced the infarct size by 21% in ischemia-reperfusion injury rats compared with that in the vehicle-treated MI/R rats.The left ventricular ejection fraction and fractional shortening were increased by 19.11% and 30.98%,respectively,in glycine-treated rats.The plasma creatine kinase levels in ischemia-reperfusion injury rats decreased following glycine treatment.Importantly,administration of glycine significantly inhibited apoptosis in post-ischemia-reperfusion myocardium,which was accompanied by suppression of phosphorylated p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase,as well as the Fas ligand.These results suggest that gly-cine attenuates myocardial ischemia-reperfusion injury in vivo by inhibiting cardiomyocytes apoptosis.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China(No.30470718)the Natural Science Foundation of Guangdong(No.04102844)the Foundation from the Bureau of Science and Technology in Guangzhou(No.2004Z-E4081).
文摘Background The classic glycine receptor （GlyR） in the central nervous system is a ligand-gated membrane-spanning ion channel. Recent studies have provided evidence for the existence of GlyR in endothelial cells, renal proximal tubular cells and most leukocytes. In contrast, no evidence for GlyR in myocardial cells has been found so far. Our recent researches have showed that glycine could protect myocardial cells from the damage induced by lipopolysaccharide （LPS）. Further studies suggest that myocardial cells could contain GlyR or binding site of glycine. Methods In isolated rat heart damaged by LPS, the myocardial monophasic action potential （MAP）, the heart rate （HR） the myocardial tension and the activities of lactate dehydrogenase （LDH） from the coronary effluent were determined. The concentration of intracellular free calcium （[Ca^2＋]i） was measured in cardiomyocytes injured by LPS and by hypoxia/reoxygenation （H/R）, which excludes the possibility that reduced calcium influx because of LPS neutralized by glycine. Immunohistochemistry was used to detect the GlyR in myocardial tissue. GlyR and its subunit in the purified cultured cardiomyocytes were identified by Western blotting. Results Although significant improvement in the MAP/MAPD20, HR, and reduction in LDH release were observed in glycine ＋ LPS hearts, myocardial tension did not recover. Further studies demonstrated that glycine could prevent rat mycordial cells from LPS and hypoxia/reoxygenation injury （no endotoxin） by attenuating calcium influx. Immunohistochemistry exhibited a positive green-fluorescence signaling along the cardiac muscle fibers. Western blotting shows that the purified cultured cardiomyocytes express GlyR β subunit, but GlyR α1 subunit could not be detected. Conclusions The results suggest that glycine receptor is expressed in cardiomyocytes and participates in cytoprotection from LPS and hypoxia/reoxygenation injury. Glycine could directly activate GlyR on the cardiomyocytes and prevent calcium influx into the cardiomyocytes.
基金supported by the National Natural Science Foundation of China(No.81070120,81000118 and 81100857)the National Basic Research Program(973 Program,No.2012CB517503 and 2011CB503903)
文摘Glycine is a well-documented cytoprotective agent.However,whether it has a protective effect against myocar-dial ischemia-reperfusion injury in vivo is still unknown.By using an open-chest anesthetized rat model,we found that glycine reduced the infarct size by 21% in ischemia-reperfusion injury rats compared with that in the vehicle-treated MI/R rats.The left ventricular ejection fraction and fractional shortening were increased by 19.11% and 30.98%,respectively,in glycine-treated rats.The plasma creatine kinase levels in ischemia-reperfusion injury rats decreased following glycine treatment.Importantly,administration of glycine significantly inhibited apoptosis in post-ischemia-reperfusion myocardium,which was accompanied by suppression of phosphorylated p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase,as well as the Fas ligand.These results suggest that gly-cine attenuates myocardial ischemia-reperfusion injury in vivo by inhibiting cardiomyocytes apoptosis.
