Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis
Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis
复制标题
DOI：
10.1002/jcp.10372
复制
发表时间：
2003-12-01
影响因子：
5.6
通讯作者：
Lotz, M
中科院分区：
文献类型：
--
作者：
Kühn, K;Shikhman, AR;Lotz, M
本研究探讨了白介素1β(IL-Ibeta)调节抗CD95抗体CH-11和蛋白酶体抑制剂(PSI)联合诱导的人软骨细胞凋亡的机制。IL-1β对细胞凋亡的影响因组织样本不同而异。IL-1β增强(16/22个样本)或抑制(6/22个样本)DNA断裂和caspase-3处理。一氧化氮(NO)合成抑制剂L精氨酸(NMMA)可阻断IL-1β的保护作用，而对细胞凋亡的刺激作用不受影响。NO供体硝普钠(SNP)和S-亚硝基-N-乙酰青霉胺(SNAP)可阻断DNA片段化，这与部分抑制caspase-3的加工有关。活性氧(ROS)清除剂吡咯烷二硫代氨基甲酸酯(PDTC)可阻断CH-11/PSI诱导的细胞凋亡和IL-1β的促进作用。IL-1β的促凋亡作用也可被p38抑制剂SB 202190消除。综上所述，IL-1β可增强CH-11/PSI诱导的大部分软骨细胞的凋亡。IL-1β的促凋亡作用不依赖于NO。相反，在少数样本中观察到的IL-1β的抗凋亡作用部分是非依赖的。(C)2003年Wiley-Liss，Inc.
This study addresses mechanisms by which interleukin-1beta (IL-Ibeta) regulates human chondrocyte apoptosis induced by a combination of the anti-CD95 antibody CH-11 and the proteasome inhibitor (PSI). The effect of IL-1beta on apoptosis varied among tissue samples. IL-1beta either enhanced (16/22 samples) or inhibited (6/22 samples) DNA fragmentation and caspase-3 processing. The protective effect of IL-1beta was abrogated by the nitric oxide (NO) synthesis inhibitor N-monomethyl-L-arginine (L-NMMA) while apoptosis stimulation was not affected. The NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl penicillamine (SNAP) blocked DNA fragmentation, and this was associated with partial inhibition of caspase-3 processing. Pyrrolidine dithiocarbamate (PDTC), a scavenger of reactive oxygen species (ROS) blocked apoptosis induction by CH-11/PSI as well as the enhancement by IL-1beta. The pro-apoptotic effects of IL-1beta were also abrogated by the p38 inhibitor SB 202190. In conclusion, IL-1beta augments CH-11/PSI induced apoptosis in the majority of chondrocyte samples. The pro-apoptotic effect of IL-1beta is not dependent on NO. In contrast, the anti-apoptotic effect of IL-1beta observed in a minority of samples is partially NO-dependent. (C) 2003 Wiley-Liss, Inc.