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Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis
Author(s) -
Kühn Klaus,
Shikhman Alexander R.,
Lotz Martin
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10372
Subject(s) - pyrrolidine dithiocarbamate , apoptosis , nitric oxide , p38 mitogen activated protein kinases , dna fragmentation , sodium nitroprusside , reactive oxygen species , chondrocyte , nitrotyrosine , chemistry , nitric oxide synthase , microbiology and biotechnology , reactive nitrogen species , biology , apoptotic dna fragmentation , biochemistry , kinase , programmed cell death , protein kinase a , nf κb , in vitro , endocrinology
This study addresses mechanisms by which interleukin‐1β (IL‐1β) regulates human chondrocyte apoptosis induced by a combination of the anti‐CD95 antibody CH‐11 and the proteasome inhibitor (PSI). The effect of IL‐1β on apoptosis varied among tissue samples. IL‐1β either enhanced (16/22 samples) or inhibited (6/22 samples) DNA fragmentation and caspase‐3 processing. The protective effect of IL‐1β 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‐1β. The pro‐apoptotic effects of IL‐1β were also abrogated by the p38 inhibitor SB 202190. In conclusion, IL‐1β augments CH‐11/PSI induced apoptosis in the majority of chondrocyte samples. The pro‐apoptotic effect of IL‐1β is not dependent on NO. In contrast, the anti‐apoptotic effect of IL‐1β observed in a minority of samples is partially NO‐dependent. J. Cell. Physiol. 197: 379–387, 2003© 2003 Wiley‐Liss, Inc.

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