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.
引用
收藏
页码:556 / 565
页数:10
相关论文
共 39 条
[21]   Sounding the alarm: Protein kinase cascades activated by stress and inflammation [J].
Kyriakis, JM ;
Avruch, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) :24313-24316
[22]   Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappa B activation prevents cell death [J].
Liu, ZG ;
Hsu, HL ;
Goeddel, DV ;
Karin, M .
CELL, 1996, 87 (03) :565-576
[23]   Apoptosis by death factor [J].
Nagata, S .
CELL, 1997, 88 (03) :355-365
[24]   Induction of apoptosis by SB202190 through inhibition of p38β mitogen-activated protein kinase [J].
Nemoto, S ;
Xiang, JL ;
Huang, S ;
Lin, AN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) :16415-16420
[25]   The p38 signal transduction pathway - Activation and function [J].
Ono, K ;
Han, JH .
CELLULAR SIGNALLING, 2000, 12 (01) :1-13
[26]   Tumor necrosis factor alpha-induced E-selectin expression is activated by the nuclear factor-kappa B and c-JUN N-terminal kinase/p38 mitogen-activated protein kinase pathways [J].
Read, MA ;
Whitley, MZ ;
Gupta, S ;
Pierce, JW ;
Best, J ;
Davis, RJ ;
Collins, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (05) :2753-2761
[27]   Mitogen-activated protein kinase pathways [J].
Robinson, MJ ;
Cobb, MH .
CURRENT OPINION IN CELL BIOLOGY, 1997, 9 (02) :180-186
[28]   Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumor necrosis factor α [J].
Roulston, A ;
Reinhard, C ;
Amiri, P ;
Williams, LT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (17) :10232-10239
[29]   Tumor necrosis factor-alpha increases ATP content in metabolically inhibited L929 cells preceding cell death [J].
SanchezAlcazar, JA ;
RuizCabello, J ;
HernandezMunoz, I ;
Pobre, PS ;
delaTorre, P ;
SilesRivas, E ;
Garcia, I ;
Kaplan, O ;
MunozYague, MT ;
SolisHerruzo, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (48) :30167-30177
[30]   RECOMBINANT HUMAN-TUMOR NECROSIS FACTOR-ALPHA - EFFECTS ON PROLIFERATION OF NORMAL AND TRANSFORMED-CELLS INVITRO [J].
SUGARMAN, BJ ;
AGGARWAL, BB ;
HASS, PE ;
FIGARI, IS ;
PALLADINO, MA ;
SHEPARD, HM .
SCIENCE, 1985, 230 (4728) :943-945