Long-term exposure to copper induces mitochondria-mediated apoptosis in mouse hearts

Ecotoxicology and Environmental Safety

Zi-wei Cheng¹  Shan Gao²  Xue-sheng Liu³  Qing-zhong Xiao⁴  Feng-qin Zhu⁵  Zi-jian Wang⁶  Ming Pan⁶  Zhi-rui Fang⁶  Kai Zhou⁶  Hua Chen⁶  Bei-bei Fu⁶  Li-jun Sun⁶  Zhu-qing Ye⁶  Chen-guang Huang⁶ 

[1]Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China

[2]Cancer Hospital, Chinese Academy of Science, Hefei 230032, China

[3]Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

[4]Clinic Medical School of Medicine, Anhui Medical University, 230031, China

[5]Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, 230022, China

[6]Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China

关键词: Copper;    Cardiomyocytes;    Mitochondria;    Apoptosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Copper is a trace element necessary for the normal functioning of organisms, but excessive copper contents may be toxic to the heart. The goal of this study was to investigate the role of excessive copper accumulation in mitochondrial damage and cell apoptosis inhibition. In vivo, the heart copper concentration and cardiac troponin I (c-TnI) and N-terminal forebrain natriuretic peptide (NT-pro-BNP) levels increased in the copper-laden model group compared to those of the control group. Histopathological and ultrastructural observations revealed that the myocardial collagen volume fraction (CVF), perivascular collagen area (PVCA) and cardiomyocyte cross-sectional area (CSA) were markedly elevated in the copper-laden model group compared with the control group. Furthermore, transmission electron microscopy (TEM) showed that the mitochondrial double-layer membrane was incomplete in the copper-laden model groups. Furthermore, cytochrome C (Cyt-C) expression was downregulated in mitochondria but upregulated in the cytoplasm in response to copper accumulation. In addition, Bcl-2 expression decreased, while Bax and cleaved caspase-3 levels increased. These results indicate that copper accumulation in cardiomyocyte mitochondria induces mitochondrial injury, and Cyt-C exposure and induces apoptosis, further resulting in heart damage.

【 授权许可】

Unknown