Liang Min, Jin Sheng, Wu Dong-Dong, Wang Ming-Jie, Zhu Yi-Chun
Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University Shanghai Medical College, Shanghai, China.
Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University Shanghai Medical College, Shanghai, China.
Nitric Oxide. 2015 Apr 30;46:114-22. doi: 10.1016/j.niox.2014.12.007. Epub 2014 Dec 15.
Hydrogen sulfide (H2S) has been reported to inhibit myocardial hypertrophy in a cell model of cardiomyocyte hypertrophy. Our previous study also shows an H2S-induced increase in glucose metabolism in insulin-targeting cells. The present study aims to examine the hypothesis that H2S attenuates myocardial hypertrophy and promotes glucose utilization in cardiomyocytes.
The cell model of cardiomyocyte hypertrophy was induced by application of phenylephrine and cardiomyocyte hypertrophy was examined using leucine incorporation assay. Protein levels were measured using Western blot analysis. The activity of related enzymes was measured with enzyme-linked immunosorbent assay (ELISA).
NaHS (an H2S donor) treatment increased the activity of cultured cardiomyocytes and reduced hypertrophy in cultured cardiomyocytes at concentrations ranging from 25 to 200 µmol/L. NaHS treatment increased glucose uptake and the efficiency of glycolysis and the citric acid cycle. The key enzymes in these reactions, including lactate dehydrogenase and pyruvate kinase and succinate dehydrogenase, were activated by NaHS treatment (100 µmol/L). Some intermediates of glycolysis and the citric acid cycle, including lactic acid, cyclohexylammonium, oxaloacetic acid, succinate, L-dimalate, sodium citrate, cis-aconitic acid, ketoglutarate and DL-isocitric acid trisodium also showed anti-hypertrophic effects in cardiomyocytes.
H2S improves glucose utilization and inhibits cardiomyocyte hypertrophy.
据报道，硫化氢（H₂S）在心肌细胞肥大的细胞模型中可抑制心肌肥大。我们之前的研究还表明，H₂S可诱导胰岛素靶向细胞的葡萄糖代谢增加。本研究旨在验证H₂S可减轻心肌肥大并促进心肌细胞葡萄糖利用这一假说。
用去氧肾上腺素诱导心肌细胞肥大的细胞模型，并用亮氨酸掺入试验检测心肌细胞肥大情况。采用蛋白质印迹分析测定蛋白质水平。用酶联免疫吸附测定法（ELISA）测量相关酶的活性。
NaHS（一种H₂S供体）处理在25至200µmol/L的浓度范围内可增加培养心肌细胞的活性并减轻其肥大。NaHS处理可增加葡萄糖摄取以及糖酵解和柠檬酸循环的效率。这些反应中的关键酶，包括乳酸脱氢酶、丙酮酸激酶和琥珀酸脱氢酶，经NaHS（100µmol/L）处理后被激活。糖酵解和柠檬酸循环的一些中间产物，包括乳酸、环己胺、草酰乙酸、琥珀酸、L-苹果酸、柠檬酸钠、顺乌头酸、酮戊二酸和DL-异柠檬酸三钠在心肌细胞中也显示出抗肥大作用。
H₂S可改善葡萄糖利用并抑制心肌细胞肥大。
