title: Protective effect of α-lipoic acid against antimycin A cytotoxicity in MC3T3-E1 osteoblastic cells.
abstract: 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.
authors: Department of Traumatic Orthopedic Surgery, The General Hospital of Ji'nan Military Command, 25 Shifan St, Jinan, Shandong Province, 250031, China.
authors: Zou
authors: Z
authors: Lin
authors: Department of Traumatic Orthopedic Surgery, The General Hospital of Ji'nan Military Command, 25 Shifan St, Jinan, Shandong Province, 250031, China.
authors: Zhang
authors: Z
authors: Guichun
authors: Department of Traumatic Orthopedic Surgery, The General Hospital of Ji'nan Military Command, 25 Shifan St, Jinan, Shandong Province, 250031, China.
authors: Liu
authors: L
authors: Lifeng
authors: Department of Traumatic Orthopedic Surgery, The General Hospital of Ji'nan Military Command, 25 Shifan St, Jinan, Shandong Province, 250031, China.
authors: Chen
authors: C
authors: Chen
authors: Department of Traumatic Orthopedic Surgery, The General Hospital of Ji'nan Military Command, 25 Shifan St, Jinan, Shandong Province, 250031, China. xccao225@126.com.
authors: Cao
authors: C
authors: Xuecheng
authors: Department of Traumatic Orthopedic Surgery, The General Hospital of Ji'nan Military Command, 25 Shifan St, Jinan, Shandong Province, 250031, China.
authors: Cai
authors: C
authors: Jinfang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000968:Antimycin A / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D020011:Protective Agents; D017382:Reactive Oxygen Species; D000968:Antimycin A; D008063:Thioctic Acid; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D003576:Electron Transport Complex IV; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Antimycin A; Mineralization; Mitochondrial dysfunction; Oxidative stress; α-Lipoic acid