Mitochondria fission accentuates oxidative stress in hyperglycemia-induced H9c2 cardiomyoblasts in vitro by regulating fatty acid oxidation

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Xiaogang Song, Chongxi Fan, Chao Wei, Wuhan Yu, Jichao Tang, Feng Ma, Yongqing Chen, Bing Wu
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Abstract

Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA (siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.

Abstract Image

线粒体裂变通过调节脂肪酸氧化作用,加剧了体外高血糖诱导的 H9c2 心肌母细胞的氧化应激。
氧化应激在糖尿病心肌病(DCM)的发病过程中起着关键作用。以往的研究表明,抑制线粒体裂变可抑制氧化应激,缓解糖尿病小鼠的线粒体功能障碍和心功能不全。然而,线粒体裂变是否会通过调节脂肪酸氧化(FAO)来加重高血糖诱导的心肌母细胞氧化应激,目前还没有研究证实。我们使用暴露于 33 毫摩尔高葡萄糖(HG)的 H9c2 心肌细胞在体外模拟 DCM。在高血糖诱导的 H9c2 心肌细胞中观察到线粒体过度分裂、细胞存活率低和脂质积累。此外,细胞还受到氧化应激损伤、三磷酸腺苷(ATP)水平降低和细胞凋亡。在暴露于 HG 的 H9c2 心肌细胞中,Dynamin 相关蛋白 1(Drp1)短干扰 RNA(siRNA)可减少靶标表达,抑制线粒体破碎和脂质积累,抑制氧化应激,减少心肌细胞凋亡,提高细胞活力和 ATP 水平,但在肉碱棕榈酰基转移酶 1(CPT1)抑制剂依托莫西处理的细胞中则没有这种作用。我们还发现,暴露于 HG 处理后,线粒体膜上 CPT1 的亚细胞定位、FAO 和烟酰胺腺嘌呤二核苷酸磷酸(NADPH)水平受到抑制,而 Drp1 siRNA 可使线粒体 CPT1、FAO 和 NADPH 恢复正常。然而,在高血糖诱导的 H9c2 心肌细胞中,用依托莫西阻断 FAO 可消除 Drp1 siRNA 的上述作用。通过 Drp1/CPT1/FAO 途径保护线粒体功能是抑制线粒体裂变以减轻高血糖诱导的 H9c2 心肌细胞氧化应激损伤的潜在机制。
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来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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