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-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.

Original languageEnglish
Pages (from-to)203-212
Number of pages10
JournalBiochemical Pharmacology
Volume66
Issue number2
DOIs
Publication statusPublished - Jul 15 2003

Fingerprint

Advanced Glycosylation End Products
Macrophages
Nitric Oxide Synthase Type II
Protein Kinase C
Genistein
Nitric Oxide
Chemical activation
Phosphoinositide Phospholipase C
Phosphorylation
Staurosporine
Protein C Inhibitor
Inositol
Threonine
Protein Kinase Inhibitors
Cytosol
Protein-Tyrosine Kinases
RAW 264.7 Cells
Protein Isoforms
Membranes

Keywords

  • Advanced glycosylation end products
  • Inducible nitric oxide synthase
  • Nitric oxide
  • Protein kinase C
  • RAW 264.7 macrophages

ASJC Scopus subject areas

  • Pharmacology

Cite this

Role of protein kinase C in BSA-AGE-mediated inducible nitric oxide synthase expression in RAW 264.7 macrophages. / Wu, Chih Hsiung; Chang, Chien Hsi; Lin, Hsiu Chen; Chen, Chien Ming; Lin, Chien-Huang; Lee, Horng Mo.

In: Biochemical Pharmacology, Vol. 66, No. 2, 15.07.2003, p. 203-212.

Research output: Contribution to journalArticle

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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-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.",
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AU - Wu, Chih Hsiung

AU - Chang, Chien Hsi

AU - Lin, Hsiu Chen

AU - Chen, Chien Ming

AU - Lin, Chien-Huang

AU - Lee, Horng Mo

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N2 - 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.

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