Effect of High Glucose on Nitric Oxide Production in Culteured Rat Mesangial Cells.
- Author:
Hyun Jin NOH
;
Hun Joo HA
;
Mi Ra YOO
;
Suk Kyun SHIN
;
Hyun Yong SONG
;
Jae Ha HWANG
;
Shin Wook KANG
;
Kyu Heon CHOI
;
Dae Seok HAN
;
Ho Young LEE
- Publication Type:Original Article
- MeSH:
Aldehyde Reductase;
Animals;
Capillary Permeability;
Diabetic Nephropathies;
Endothelial Cells;
Glucose*;
Kidney Failure, Chronic;
Mesangial Cells*;
Nitric Oxide*;
Protein Kinases;
Rats*;
RNA, Messenger
- From:Korean Journal of Nephrology
1999;18(6):856-868
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Diabetic nephopathy is one of the leading causes of end-stage renal disease and characterized pathologically by the glomerular mesangial expansion and increased extracellular matrix(ECM) formation. Glomerular hyper-filtration and increased vascular permeability observed in the early stage of diabetic nephropathy have been proposed to play a significant pathophysiologic role in the eventual development of glomerulosclerosis of dia-betic nephropathy. Some studies have suggested that this glomerular hyperfiltration is mediated by increased nitric oxide(NO) production via the constitutive nitric oxide synthase(cNOS) pathway present in endothelial cells under the high glucose environment. However, the exact role of the inducible NOS(iNOS) pathway present in mesangial cells in the pathogenesis of diabetic neph-ropathy is not clearly established. The present study was carried out to examine whether NO production via the iNOS pathway is mo-dulated in cultured rat mesangial cells exposed to the high glucose environment and underlying mechanism of this modulation. For this purpose, the production of the stable metabolite of NO(nitrite), intracellular cyclic gu-anosine monophosphate(cGMP), iNOS mRNA expression and iNOS protein synthesis were examined under different glucose concentrations. Rat mesangial cells cultured in high glucose concen- tration(30mM D-glucose) increased significantly nitrit#e/ nitrate production and intracellular cGMP levels upon stimulation with lipopolysaccharide(LPS) plus interfer-on-r (IFN-r ) compared with control glucose concen- tration(5.6mM D-glucose). Mesangial iNOS mRNA expression and protein synthesis also increased signifi- cantly in response to high glucose. This enhanced iNOS mRNA expression induced by high glucose concentration was significantly suppressed by protein kinase C(PKC) inhibitor, calphostin C, and the aldose reductase inhibitor, 6-bromo-l, 3-dioxo-1H- benz[d, elisoquinoline-2(3H)-acetic acid. These results indicate that high glucose in combination with stimulation by LPS plus IFN- r enhances NO production from mesangial cells by the iNOS pathway, and that the activation of PKC and the polyol pathway may play a role in this enhancement.
