Mechanism of increased angiotensin II levels in glomerular mesangial cells cultured in high glucose

被引:123
作者
Singh, R
Singh, AK
Alavi, N
Leehey, DJ
机构
[1] Vet Affairs Hosp, Dept Med, Hines, IL 60141 USA
[2] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA
[3] Hektoen Inst Med Res, Chicago, IL 60612 USA
[4] Vet Affairs Hosp, Dept Med, Chicago, IL USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2003年 / 14卷 / 04期
关键词
D O I
10.1097/01.ASN.0000060804.40201.6E
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Previous studies have shown that glucose increases angiotensin II (AngII) levels in rat glomerular mesangial cells and that AngII mediates the inhibitory effects of high glucose on matrix degradation in these cells. The present study addresses the following questions: (1) What are the mechanisms for the generation of AngII in mesangial cells? (2) What are the effects of glucose on AngII generation by these mechanisms? Experiments employed primary mesangial cells from normal Sprague-Dawley rats. The levels of immunoreactive angiotensinogen (AGT), angiotensin I (AngI), and angiotensin II (AngII) were measured by ELISA. AGT mRNA expression was determined by Northern blot analysis. Incubation of cells for 24 h in high glucose (30 mM) increased AGT levels by 1.5-fold and increased AGT mRNA expression; this was accompanied by a 1.5-fold increment in AngI and 1.7-fold increment in AngII levels. Renin activity (measured as AngI generation in the presence of excess AGT) and ACE levels and activity were not altered by high glucose. In further experiments, the effect of high glucose on formation of Ang peptides from exogenous AngI in mesangial cell extracts was examined using HPLC. Exogenous AngI was converted into various Ang peptides, including AngII, Ang(1-9), Ang(1-7), and Ang(3-8). A significant increase in formation of AngII from AngI was observed in cells incubated in high glucose. In addition, AngII production from exogenous Ang(1-9) in cell extracts was also stimulated by high glucose. These findings demonstrate that glucose increases mesangial AngII levels via an increase in AGT and AngI. In addition, this study provides new information that Ang(1-9) is produced by mesangial cells, can be converted to AngII, and that this conversion is also stimulated under high-glucose conditions.
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页码:873 / 880
页数:8
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