p38 kinase-dependent and -independent Inhibition of protein kinase C zeta and -alpha regulates nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes.
J Biol Chem
; 277(33): 30375-81, 2002 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-12048219
ABSTRACT
In articular chondrocytes, nitric oxide (NO) production triggers dedifferentiation and apoptotic cell death that is regulated by the converse functions of two mitogen-activated protein kinase subtypes, extracellular signal-regulated kinase (ERK) and p38 kinase. Since protein kinase C (PKC) transduces signals that influence differentiation, survival, and apoptosis of various cell types, we investigated the roles and underlying molecular mechanisms of action of PKC isoforms in NO-induced dedifferentiation and apoptosis of articular chondrocytes. We report here that among the expressed isoforms, activities of PKCalpha and -zeta were reduced during NO-induced dedifferentiation and apoptosis. Inhibition of PKCalpha activity was independent of NO-induced activation of ERK or p38 kinase and occurred due to blockage of expression. On the other hand, PKCzeta activity was inhibited as a result of NO-induced p38 kinase activation and was observed prior to proteolytic cleavage by a caspase-mediated process to generate enzymatically inactive fragments. Inhibition of PKCalpha or -zeta activities potentiated NO-induced apoptosis, whereas ectopic expression of these isoforms significantly reduced the number of apoptotic cells and blocked dedifferentiation. Ectopic expression of PKCalpha or -zeta did not affect p38 kinase or ERK but inhibited the p53 accumulation and caspase-3 activation that are required for NO-induced apoptosis of chondrocytes. Therefore, our results collectively indicate that p38 kinase-independent and -dependent inhibition of PKCalpha and -zeta, respectively, regulates NO-induced apoptosis and dedifferentiation of articular chondrocytes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
/
Cartilagem Articular
/
Diferenciação Celular
/
Apoptose
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Proteínas Quinases Ativadas por Mitógeno
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Isoenzimas
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2002
Tipo de documento:
Article