Abstract

Advanced glycosylation end products (AGEs) have been implicated in the pathogenesis of diabetic complications. Treatment of RAW 264.7 macrophages with bovine serum albumin (BSA)-derived AGEs caused dose- and time-dependent increases in nitrite production and inducible nitric oxide synthase (iNOS) expression. These effects were blocked by the nuclear factor-kappa B (NF-κB) inhibitor, pyrrolidone dithiocarbamate (PDTC). BSA-AGEs also stimulated the translocation of p65 NF-κB from cytosol to the nucleus. Electrophoretic mobility shift assay revealed that the NF-κB DNA-protein-binding activity was enhanced by AGEs. The tyrosine kinase inhibitor, genistein, the phosphatidylinositol-3-kinase (PI 3-K) inhibitor, LY 294002, the protein kinase C (PKC) inhibitor, Ro 31-8220, and the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB 203580, all inhibited AGEs-stimulated iNOS expression, NO release, NF-κB translocation and NF-κB DNA binding activity. These results suggest that AGEs may activate NF-κB via an upstream signaling cascade composed of tyrosine kinase, PI 3-K, PKC, and p38 MAPK, resulting in the induction of iNOS expression in RAW 264.7 macrophages.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume194
Issue number1-2
DOIs
Publication statusPublished - Aug 30 2002

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Advanced Glycosylation End Products
NF-kappa B
Nitric Oxide Synthase Type II
Phosphatidylinositol 3-Kinase
Macrophages
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Bovine Serum Albumin
Protein-Tyrosine Kinases
Protein Kinase C
Pyrrolidinones
Electrophoretic mobility
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Protein C Inhibitor
Genistein
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Diabetes Complications
Nitrites
Cytosol

Keywords

  • Advanced glycosylation end products
  • Inducible nitric oxide synthase
  • Nuclear factor-kappa B
  • RAW 264.7 macrophages

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Advanced glycosylation end products induce NF-κB dependent iNOS expression in RAW 264.7 cells. / Wu, Chih Hsiung; Huang, Chao Ming; Lin, Chien-Huang; Ho, Yuan Sun; Chen, Chien Ming; Lee, Horng Mo.

In: Molecular and Cellular Endocrinology, Vol. 194, No. 1-2, 30.08.2002, p. 9-17.

Research output: Contribution to journalArticle

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