Department of Life Science, J.B. Campus, Bangalore University, Bengaluru, Karnataka, India.
Laboratory of Gerontology, Department of Zoology, J.B. Campus, Bangalore University, Bengaluru, Karnataka, India.
IUBMB Life. 2019 Dec;71(12):1876-1895. doi: 10.1002/iub.2133. Epub 2019 Jul 30.
Redox imbalance due to hyperglycemia is a causative factor for an increased generation of reactive oxygen species (ROS) that leads to mitochondrial dysfunction and the release of cytochrome-c. The aim of the present study is to elucidate the functional role of oxidative stress (OS) in the induction of apoptosis in H9c2 cells in the hyperglycemic state through glucose transporter-4 (GLUT-4) regulation and antioxidant status. H9c2 cells were incubated with 15, 24, and 33 mM glucose for 24, 48, and 72 hr to induce hyperglycemic stress. Hyperglycemic episodes have significantly influenced GLUT-4 mRNA regulation, depleted glutathione (GSH) and its associated enzymes, reduced cellular antioxidant enzymes (AOEs), caused nuclear condensation, and induced apoptosis by activating caspase-9 and 3 and annexin V binding in a concentration and duration-dependent manner. Trolox pretreatment significantly enhanced the GLUT-4 mRNA and antioxidant defense mechanism, suppressed nuclear condensation, and prevented cytochrome-c release, thereby reducing mitochondrial-dependent apoptosis. The present study shows that the toxic effect of high glucose is significantly regulated and that OS induction can be prevented through a water-soluble vitamin E analog "Trolox" treatment.
由于高血糖导致的氧化还原失衡是活性氧（ROS）生成增加的一个原因，这会导致线粒体功能障碍和细胞色素-c 的释放。本研究旨在通过葡萄糖转运蛋白-4（GLUT-4）调节和抗氧化状态来阐明氧化应激（OS）在诱导高糖状态下 H9c2 细胞凋亡中的功能作用。将 H9c2 细胞在 15、24 和 33mmol/L 葡萄糖中孵育 24、48 和 72 小时以诱导高血糖应激。高血糖发作显著影响 GLUT-4 mRNA 调节，耗竭谷胱甘肽（GSH）及其相关酶，降低细胞抗氧化酶（AOEs），导致核浓缩，并通过激活 caspase-9 和 3 以及依赖浓度和时间的方式与膜联蛋白 V 结合诱导细胞凋亡。Trolox 预处理显著增强了 GLUT-4 mRNA 和抗氧化防御机制，抑制了核浓缩，并防止了细胞色素-c 的释放，从而减少了线粒体依赖性凋亡。本研究表明，高葡萄糖的毒性作用受到显著调节，并且可以通过水溶性维生素 E 类似物“Trolox”治疗来预防 OS 诱导。
