SOCS-1 inhibits TNF-alpha-induced cardiomyocyte apoptosis via ERK1/2 pathway activation

作者：Yan Ling; Tang Qizhu^*; Shen Difei; Peng Sheng; Zheng Qian; Guo Haipeng; Jiang Ming; Deng Wei

来源：Inflammation, 2008, 31(3): 180-188.

DOI：10.1007/s10753-008-9063-5

• tumor necrosis factor
• apoptosis
• cardiomyocyte
• signal transduction

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-a. However, whether SOCS-I 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-I 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-I prevents TNF-alpha-induced apoptosis in cardiac myocytes via ERK1/2 pathway activation.

• 出版日期2008-6
• 单位武汉大学