Protein kinase Cα and ζ regulate nitric oxide-induced NF-κB activation that mediates cyclooxygenase-2 expression and apoptosis but not dedifferentiation in articular chondrocytes

被引:48
作者
Kim, SJ [1 ]
Chun, JS [1 ]
机构
[1] Kwangju Inst Sci & Technol, Dept Life Sci, Buk Gu, Gwangju 500712, South Korea
关键词
nitric oxides protein kinase C; NF-kappa B; apoptosis; dedifferentiation; COX-2;
D O I
10.1016/S0006-291X(03)00305-X
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
Nitric oxide (NO) regulates differentiation, survival, and cyclooxygenase (COX)-2 expression in articular chondrocytes. NO-induced apoptosis and dedifferentiation are mediated by p38 kinase activity and p38 kinase-independent and -dependent inhibition of protein kinase C (PKC)alpha and zeta. Because p38 kinase also activates NF-kappaB, we investigated the functional relationship between PKC and NF-kappaB signaling and the role of NF-kappaB in apoptosis, dedifferentiation, and COX-2 expression. We found that NO-stimulated NF-kappaB activation was inhibited by ectopic PKCalpha and zeta expression, whereas NO-stimulated inhibition of PKCalpha and zeta activity was not affected by NF-kappaB inhibition. Inhibition of NO-induced NF-kappaB activity did not affect inhibition of type II collagen expression but did abrogate COX-2 expression and apoptosis. Taken together, our results indicate that NO-induced inhibition of PKCalpha and activity is required for the NF-kappaB activity that regulates apoptosis and COX-2 expression but not dedifferentiation in articular chondrocytes. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:206 / 211
页数:6
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