Protein kinase C alpha and zeta regulate nitric oxide-induced NF-kappa B activation that mediates cyclooxygenase-2 expression and apoptosis but not dedifferentiation in articular chondrocytes.
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-kappa B, we investigated the functional relationship between PKC and NF-kappa B signaling and the role of NF-kappa B in apoptosis, dedifferentiation, and COX-2 expression. We found that NO-stimulated NF-kappa B activation was inhibited by ectopic PKC alpha and zeta expression, whereas NO-stimulated inhibition of PKC alpha and zeta activity was not affected by NF-kappa B inhibition. Inhibition of NO-induced NF-kappa B 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 PKC alpha and zeta activity is required for the NF-kappa B activity that regulates apoptosis and COX-2 expression but not dedifferentiation in articular chondrocytes.
Kim
Song-Ja
SJ
Department of Life Science, Kwangju Institute of Science and Technology, Buk-Gu, Gwangju 500-712, South Korea.
Chun
Jang-Soo
JS
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000473:pathology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D011233:Precipitin Tests; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D011817:Rabbits; D048051:p38 Mitogen-Activated Protein Kinases; D000099221:Protein Kinase C zeta
D053148:Caspase 3; D020169:Caspases; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007527:Isoenzymes; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099221:Protein Kinase C zeta