tailieunhanh - Báo cáo khoa học: Mitochondrial chaperone tumour necrosis factor receptor-associated protein 1 protects cardiomyocytes from hypoxic injury by regulating mitochondrial permeability transition pore opening

Tumour necrosis factor receptor-associated protein 1 (TRAP1) is a mito-chondrial chaperone that plays a role in maintaining mitochondrial func-tion and regulating cell apoptosis. The opening of the mitochondrial permeability transition pore (MPTP) is a key step in cell death after hypoxia. | Mitochondrial chaperone tumour necrosis factor receptor-associated protein 1 protects cardiomyocytes from hypoxic injury by regulating mitochondrial permeability transition pore opening Fei Xiang Yue-Sheng Huang Xiao-Hua Shi and Qiong Zhang Institute of Burn Research State Key Laboratory of Trauma Burns and Combined Injury Southwest Hospital Third Military Medical University Chongqing China Keywords cardiomyocytes cell damage hypoxia mitochondrialpermeability transition pore tumour necrosis factor receptor-associated protein 1 Correspondence . Huang Institute of Burn Research State Key Laboratory of Trauma Burns and Combined Injury Southwest Hospital Third Military MedicalUniversity Chongqing 400038 China Fax 86 23 65461696 Tel 86 23 65461696 E-mail Received 3 December 2009 revised 3 February 2010 accepted 11 February 2010 doi Tumour necrosis factor receptor-associated protein 1 TRAP1 is a mitochondrial chaperone that plays a role in maintaining mitochondrial function and regulating cell apoptosis. The opening of the mitochondrial permeability transition pore MPTP is a key step in cell death after hypoxia. However it is still unclear whether TRAP1 protects cardiomyocytes from hypoxic damage by regulating the opening of the pore. In the present study primary cultured cardiomyocytes from neonatal rats were used to investigate changes in TRAP1 expression after hypoxia treatment as well as the mechanism and effect of TRAP1 on hypoxic damage. The results obtained showed that TRAP1 expression increased after 1 h of hypoxia and continued to increase for up to 12 h of treatment. Hypoxia caused an increase in cell death and decreased cell viability and mitochondrial membrane potential overexpressing TRAP1 prevented hypoxia-induced damage to cardiomyocytes. The silencing of TRAP1 induced an increase in cell death and decreased both cell viability and mitochondrial membrane potential in cardiomyocytes under normoxic