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P38β MAP kinase protects rat mesangial cells from TNF-α-induced apoptosis
被引:29
作者:
Guo, YL
Kang, BB
Han, JH
Williamson, JR
机构:
[1] Temple Univ, Sch Med, Sol Sherry Thrombosis Res Ctr, Philadelphia, PA 19140 USA
[2] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA
[3] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词:
protein kinase;
ERK;
JNK;
NF-kappa B;
apoptosis;
D O I:
10.1002/jcb.1180
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
p38 MAP kinases (p38) and c-Jun N-terminal protein kinases (INK) have been associated with TNF-alpha -induced apoptosis. However, recent studies indicate that an early but brief activation of INK and/or p38 may actually protect some cells from TNF-alpha -induced apoptosis. Whether the activation of INK and p38 provides a pro- or anti-apoptotic signal for TNF-alpha has been controversial. In this study, we investigated the role of p38 in the regulation of TNF-alpha cytotoxicity in rat mesangial cells. Treatment of the cells with TNF-alpha alone had little effect on their viability, but they became very sensitive to apoptosis when treated with TNF-alpha in the presence of the p38 inhibitor SB 203580. These results suggested that the p38 pathway is critical for mesangial cells to survive the toxic effect of TNF-alpha. Using adenovirus-mediated gene transfer technique, we further demonstrated that p38 beta, but not p38 alpha, is essential to protect the cells from TNF-alpha toxicity. It has been speculated that there is a synergetic interaction between the p38 and the nuclear factor-kappaB (NF-kappaB) pathways in protecting certain cells from apoptosis. However, expression of neither p38 beta nor its dominant negative mutant in mesangial cells interfered with TNF-alpha -induced translocation of NF-kappaB, the initial step of NF-kappaB activation. While it is unclear whether p38 beta regulates NF-kappaB transcription activity at other steps, it is apparent that p38 beta does not affect TNF-alpha -induced NF-kappaB activation at the stage of nuclear translocation. (C) 2001 Wiley-Liss, Inc.
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页码:556 / 565
页数:10
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