Zhao 2019 Basic Res Cardiol
|Zhao J, Gao JL, Zhu JX, Zhu HB, Peng X, Jiang M, Fu Y, Xu J, Mao XH, Hu N, Ma MH, Dong DL (2019) The different response of cardiomyocytes and cardiac fibroblasts to mitochondria inhibition and the underlying role of STAT3. Basic Res Cardiol 114:12.|
Abstract: Cardiomyocyte loss and cardiac fibrosis are the main characteristics of cardiac ischemia and heart failure, and mitochondrial function of cardiomyocytes is impaired in cardiac ischemia and heart failure, so the aim of this study is to identify fate variability of cardiomyocytes and cardiac fibroblasts with mitochondria inhibition and explore the underlying mechanism. The mitochondrial respiratory function was measured by using Oxygraph-2k high-resolution respirometry. The STAT3 expression and activity were evaluated by western blot. Cardiomyocytes and cardiac fibroblasts displayed different morphology. The mitochondrial respiratory function and the expressions of mitochondrial complex I, II, III, IV, and V of cardiac fibroblasts were lower than that of cardiomyocytes. Mitochondrial respiratory complex I inhibitor rotenone and H2O2 (100 µM, 4 h) treatment induced cell death of cardiomyocyte but not cardiac fibroblasts. The function of complex I/II was impaired in cardiomycytes but not cardiac fibroblasts stimulated with H2O2 (100 µM, 4 h) and in ischemic heart of mice. Rotenone and H2O2 (100 µM, 4 h) treatment reduced STAT3 expression and activity in cardiomyocytes but not cardiac fibroblasts. Inhibition of STAT3 impaired mitochondrial respiratory capacity and exacerbated H2O2-induced cell injury in cardiomycytes but not significantly in cardiac fibroblasts. In conclusion, the different susceptibility of cardiomyocytes and cardiac fibroblasts to mitochondria inhibition determines the cell fate under the same pathological stimuli and in which STAT3 plays a critical role.
• Keywords: Cardiac fibroblasts, Cardiomyocytes, H2O2, Mitochondria, STAT3 • Bioblast editor: Plangger M
Labels: MiParea: Respiration
Stress:Ischemia-reperfusion Organism: Rat Tissue;cell: Heart, Fibroblast Preparation: Intact cells, Permeabilized cells Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k