Glycine Protects H9C2 Cardiomyocytes from High Glucose- and Hypoxia/Reoxygenation-Induced Injury via Inhibiting PKCβ2 Activation and Improving Mitochondrial Quality.
Glycine Protects H9C2 Cardiomyocytes from High Glucose- and Hypoxia/Reoxygenation-Induced Injury via Inhibiting PKCβ2 Activation and Improving Mitochondrial Quality.
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甘氨酸通过抑制 PKCβ2 激活和改善线粒体质量来保护 H9C2 心肌细胞免受高血糖和缺氧/复氧引起的损伤
DOI：
10.1155/2018/9502895
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发表时间：
2018
影响因子：
4.3
通讯作者：
Lei S
中科院分区：
文献类型：
--
作者：
Zhang Y;Su W;Zhang Q;Xu J;Liu H;Luo J;Zhan L;Xia Z;Lei S
糖尿病患者心肌缺血再灌注损伤（IRI）的发生与PKCβ2激活和线粒体功能障碍有关。甘氨酸已被证明是一种细胞保护剂，以减轻糖尿病相关的异常和减少心肌IRI，但其潜在的机制仍不清楚。本研究旨在探讨甘氨酸是否能通过抑制PKCβ2的活化和改善线粒体质量来减轻高糖（HG-）和缺氧/复氧（H/R-）诱导的H9 C2细胞损伤。 将H9 C2细胞暴露于低糖（LG）或高糖（HG）条件下，同时加入或不加入甘氨酸或PKCβ2选择性抑制剂CGP 53353处理48 h，然后缺氧4 h，再复氧2 h（H/R）。采用相应的试剂盒检测细胞活力、乳酸脱氢酶（LDH）释放、线粒体膜电位（MMP）、超氧化物歧化酶（SOD）活性和丙二醛（MDA）浓度。Western blot检测线粒体质控相关蛋白（LC-3 II、Mfn-2、Cyt-C）及PKCβ2活性。 与LG组相比，HG刺激可显著降低细胞活力和SOD活性，增加LDH释放、MDA生成和PKCβ2活性，H/R损伤可进一步增加上述变化。甘氨酸或CGP 53353处理可显著降低HG和H/R刺激引起的LDH释放、MDA生成、PKCβ2活化和Cyt-C表达的增加以及细胞活力、SOD活性、MMP、Mfn-2表达和LC-3 II/LC-3 I比值的降低。 补充甘氨酸通过抑制PKCβ2活化和改善线粒体质量保护H9 C2细胞免受HG和H/R诱导的细胞损伤。
Patients with diabetes are more vulnerable to myocardial ischemia reperfusion injury (IRI), which is involved in PKCβ2 activation and mitochondrial dysfunction. Glycine has been documented as a cytoprotective agent to attenuate diabetes-related abnormalities and reduce myocardial IRI, but the underlying mechanisms are still unclear. We determined whether glycine could attenuate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by inhibiting PKCβ2 activation and improving mitochondrial quality in cultured H9C2 cells. H9C2 cells were either exposed to low glucose (LG) or HG conditions with or without treatment of glycine or CGP53353 (a selective inhibitor of PKCβ2) for 48 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). Cell viability, lactate dehydrogenase (LDH) release, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration were detected using corresponding commercial kits. Mitochondrial quality control-related proteins (LC-3II, Mfn-2, and Cyt-C) and PKCβ2 activation were detected by Western blot. HG stimulation significantly decreased cell viability and SOD activity and increased LDH release, MDA production, and PKCβ2 activation as compared to LG group, all of which changes were further increased by H/R insult. Glycine or CGP53353 treatment significantly reduced the increase of LDH release, MDA production, PKCβ2 activation, and Cyt-C expression and the decrease of cell viability, SOD activity, MMP, Mfn-2 expression, and LC-3II/LC-3I ratio induced by HG and H/R stimulation. Supplementary glycine protects H9C2 cells from HG- and H/R-induced cellular injury by suppressing PKCβ2 activation and improving mitochondria quality.
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影响因子：
9.3
作者：
Adams B;Mapanga RF;Essop MF
通讯作者：
Essop MF
影响因子：
4.6
作者：
Liao WI;Lin CS;Lee CH;Wu YC;Chang WC;Hsu CW;Wang JC;Tsai SH
通讯作者：
Tsai SH
影响因子：
5
作者：
Liang Q;Kobayashi S
通讯作者：
Kobayashi S
DOI：
10.1152/ajplung.00155.2013
发表时间：
2014-05-01
影响因子：
4.9
作者：
Aravamudan, Bharathi;Kiel, Alexander;Prakash, Y. S.
通讯作者：
Prakash, Y. S.
影响因子：
2.7
作者：
Meng, Guang-Xing;Yuan, Qiang;Wang, Yi-Jun
通讯作者：
Wang, Yi-Jun