SOCS-1 Inhibits TNF-alpha-Induced Cardiomyocyte Apoptosis via ERK1/2 Pathway Activation.
SOCS-1 Inhibits TNF-alpha-Induced Cardiomyocyte Apoptosis via ERK1/2 Pathway Activation.
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in mitogen-activated protein kinase (MAPK) signaling pathways, contributes to the pathogenesis of cardiovascular diseases. Recently, suppressor of cytokine signaling-1 (SOCS-1) has been shown to modulate responses to TNF-alpha. However, whether SOCS-1 suppresses TNF-alpha-dependent apoptotic processes in cardiomyocytes and whether MAPK pathways mediate this effect have not been clearly elucidated. This study was carried out to define the role of SOCS-1 on TNF-alpha-induced apoptosis in neonatal rat cardiomyocytes and to investigate the signal pathways involved. Exposure to TNF-alpha (10 ng/ml for 24 h) significantly increased the number of apoptotic cells, the activity of caspase-8 and caspase-3, and the Bax/Bcl-xl ratio. In contrast, adenovirus-mediated gene transfer of SOCS-1 reversed the pro-apoptotic effect of TNF-alpha. Additionally, preincubation of cardiomyocytes with the extracellular signal-regulated kinase-1 and -2 (ERK1/2) inhibitor PD98059 attenuated the protective effect of SOCS-1, but the p38-MAPK inhibitor SB203580 and the c-Jun amino-terminal kinase (JNK) inhibitor SP600125 had no effect. Furthermore, the TNF-alpha-induced decrease in the phosphorylation of ERK1/2 was abolished by overexpression of SOCS-1. These findings suggest that SOCS-1 prevents TNF-alpha-induced apoptosis in cardiac myocytes via ERK1/2 pathway activation.
Yan L, Tang Q, Shen D, Peng S, Zheng Q, Guo H, Jiang M, Deng W.
Department of Cardiology, Renmin Hospital of Wuhan University School of Medicine, 238 JieFang Road, Wuchang, Wuhan, 430060, People’s Republic of China.