Abstract
Tumor necrosis factor-alpha (TNF-α), 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-α. However, whether SOCS-1 suppresses TNF-α-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-α-induced apoptosis in neonatal rat cardiomyocytes and to investigate the signal pathways involved. Exposure to TNF-α (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-α. 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-α-induced decrease in the phosphorylation of ERK1/2 was abolished by overexpression of SOCS-1. These findings suggest that SOCS-1 prevents TNF-α-induced apoptosis in cardiac myocytes via ERK1/2 pathway activation.
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Abbreviations
- SOCS-1:
-
suppressor of cytokine signaling-1
- TNF-α:
-
tumor necrosis factor-alpha
- ERK1/2:
-
extracellular signal-regulated kinase-1 and -2
- MAPK:
-
mitogen-activated protein kinase
- JNK:
-
c-Jun amino-terminal kinase
- JAK:
-
Janus kinase
- STAT:
-
signal transducers and activators of transcription
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Acknowledgments
We would like to thank Professor Akihiko Yoshimura for providing pFLAG-CMV2-SOCS-1 plasmid. This work was supported by the Specialized Research Fund for the Doctoral Program of Higher Education in China (No.20070486103).
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Yan, L., Tang, Q., Shen, D. et al. SOCS-1 Inhibits TNF-α-Induced Cardiomyocyte Apoptosis via ERK1/2 Pathway Activation. Inflammation 31, 180–188 (2008). https://doi.org/10.1007/s10753-008-9063-5
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DOI: https://doi.org/10.1007/s10753-008-9063-5