Role of Protein Kinase C in
BSA-AGE-Mediated inducible Nitric Oxide
Synthase Expression in RAW 264.7
Macrophages
吳志雄
Wu CH;Chang CH;Lin HC;Chen CM;Lin CH;Lee HM
摘要
Abstract
In the present study, the roles of protein kinase C (PKC) in BSA-derived advanced glycosylation end products (BSA-AGEs)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were
investigated. Treatment of RAW 264.7 cells with BSA-AGEs caused dose- and time-dependent increases in NO release and iNOS expression in RAW 264.7 cells, whereas BSA alone had no effect on iNOS induction. The tyrosine kinase inhibitor (genistein), the phosphatidylinositol-specific phospholipase C inhibitor (U-73122), the phosphatidylcholine-specific phospholipase C inhibitor (D-609). and the PKC inhibitors (staurosporine, Ro 31-8220, and Go 6976) all inhibited BSA-AGE-induced NO release and iNOS expression in RAW 264.7 cells.
Stimulation of RAW 264.7 cells with BSA-AGEs resulted in the formation of inositol monophosphate; the response was attenuated by U-73122 and
genistein. BSA-AGEs stimulated PKC-a, -β1, -6, and -η but not -ξ translocation from the cytosol to the membrane. However, incubation of RAW 264.7 cells with BSA-AGEs increased phosphorylation of PKC-ξ at threonine-410, which reflects activation of PKC-ξ, indicating the possible involvement of these PKC isoforms in AGE-mediated effects. Pretreatment of RAW 264.7 cells with U-73122, D-609, and genistein reduced the AGE-stimulated translocation of PKC-α, -β1, -δ, and -η and activation of PKC-ξ. Taken together, these data suggest that BSA-AGEs might activate PKC and subsequently induce iNOS expression and NO release
