Enhanced expression of inducible nitric oxide synthase in murine macrophages and glomerular mesangial cells by elevated glucose levels: Possible mediation via protein kinase C+

Kumar Sharma, Theodore M. Danoff, Andrew DePiero, Fuad N. Ziyadeh

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Increased blood flow and vascular permeability of early diabetes have been associated with increased nitric oxide formation in diabetic rats, but the specific nitric oxide synthase responsible is unknown. We examined the modulation of the induction and activity of the inducible NOS isoform by high glucose concentration in a murine macrophage cell line, RAW 264.7, and murine glomerular mesangial cells. Culturing both cell types in high glucose concentration led to significant increases in nitrite production and the mRNA encoding iNOS upon stimulation with LPS plus interferon-γ, as compared with normal glucose concentration. High glucose also modestly enhanced LPS/IFN-γ-induced stimulation of the iNOS promoter in transient transfection experiments in mesangial cells. Protein kinase C activation led to enhanced mRNA expression of iNOS, and inhibitors of protein kinase C blocked nitrite accumulation in mesangial cells. These findings suggest that high glucose in combination with stimulation by LPS plus IFN-γ enhances iNOS expression, and protein kinase C activation may be playing a role in this enhancement.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume207
Issue number1
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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