Role of protein kinase C in BSA-AGE-mediated inducible nitric oxide synthase expression in RAW 264.7 macrophages

Chih Hsiung Wu, Chien Hsi Chang, Hsiu Chen Lin, Chien Ming Chen, Chien-Huang Lin, Horng Mo Lee

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

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-α, -βI, -δ, and -η but not -ζ translocation from the cytosol to the membrane. However, incubation of RAW 264.7 cells with BSA-AGEs increased phosphorylation of PKC-ζ at threonine-410, which reflects activation of PKC-ζ, 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, -βI, -δ, and -η and activation of PKC-ζ. Taken together, these data suggest that BSA-AGEs might activate PKC and subsequently induce iNOS expression and NO release.
原文英語
頁(從 - 到)203-212
頁數10
期刊Biochemical Pharmacology
66
發行號2
DOIs
出版狀態已發佈 - 七月 15 2003

ASJC Scopus subject areas

  • Pharmacology

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