Protective effect of α-lipoic acid against antimycin A cytotoxicity in MC3T3-E1 osteoblastic cells

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• 作者：Zou Lin ; Zhang Guichun ; Liu Lifeng ; Chen Chen ; Cao Xuecheng…
• 关键词：Antimycin A ; α ; Lipoic acid ; Mineralization ; Oxidative stress ; Mitochondrial dysfunction
• 刊名：Cell Stress and Chaperones
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：22
• 期：1
• 页码：5-13
• 全文大小：
• 刊物主题：Biomedicine, general; Cell Biology; Biochemistry, general; Immunology; Cancer Research; Neurosciences;
• 出版者：Springer Netherlands
• ISSN：1466-1268
• 卷排序：22

文摘

Oxidative stress represents a major cause of cellular damage and death in the process of osteoporosis. Antimycin A (AMA) has been shown to stimulate mitochondrial superoxide anions and reactive oxygen species (ROS). α-Lipoic acid (α-LA) is a naturally occurring essential coenzyme in mitochondrial multienzyme complexes and acts as a key player in mitochondrial energy production. However, whether α-LA affects the cytotoxicity of AMA in osteoblastic cells is unknown. In this study, we investigated the protective effects of α-LA against AMA-induced cytotoxicity using the MC3T3-E1 osteoblast-like cell line. Our results indicated that α-LA treatment attenuated AMA-induced cytotoxicity and LDH release in a dose-dependent manner. Notably, a significant recovery effect of α-LA on mineralization inhibited by AMA was found. Our results also demonstrated that treatment with 50 μM AMA leads to a reduction of mitochondrial membrane potential (MMP) and the complex IV dysfunction, which was inhibited by pretreatment with α-LA in a dose-dependent manner. In addition, treatment with α-LA significantly reduced the generation of ROS and mitochondrial superoxide production induced by AMA. In addition, our result suggests that PI3K/Akt and CREB pathways are related to the protective effect of α-LA. Importantly, Hoechst 33258 staining results indicated that pretreatment with α-LA prevented AMA-induced apoptosis. Mechanistically, we found that α-LA prevents MC3T3-E1 cells from apoptosis through attenuating cytochrome C release and reducing the level of cleaved caspase-3.