Effect of high glucose on superoxide in human mesangial cells: Role of angiotensin

被引:20
作者
Leehey, DJ
Isreb, MA
Marcic, S
Singh, AK
Singh, R
机构
[1] Vet Affairs Hosp, Hines, IL 60141 USA
[2] Loyola Univ, Med Ctr, Maywood, IL 60153 USA
[3] Hektoen Inst Med Res, Chicago, IL 60612 USA
来源
NEPHRON EXPERIMENTAL NEPHROLOGY | 2005年 / 100卷 / 01期
关键词
high glucose; angiotensin II; NADH/NADPH oxidase; superoxide; superoxide dismutase;
D O I
10.1159/000084348
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
Background/Aims: Reactive oxygen species, and especially superoxide (O-2(radical anion)), have been implicated in diabetic nephropathy. O-2(radical anion) accumulation in cells is dependent on O-2(radical anion) production (by NADH/NADPH oxidase) as well as scavenging by superoxide dismutase ( SOD) activity. This study was designed to investigate the effects of high glucose (HG) on O-2(radical anion) accumulation and SOD activity in human mesangial cells (HMC) and to determine if these effects are mediated by angiotensin II (Ang II). Methods: HMC were incubated in media containing 10 m M glucose ( control, C), 30 m M glucose ( HG), 10 m M glucose + either 20 m M 2-deoxy-D-glucose (2-DG) or 20 m M mannitol ( high mannitol, HM) ( osmotic controls), or Ang II (10(-5) M). Ang II action was antagonized by employing 10(-4) M of Ang II receptor antagonists (losartan or irbesartan) or 10(-4) M of NADH/NADPH oxidase inhibitors [ diphenyleneiodonium chloride (DPI) or apocynin]. Superoxide and total SOD activity were assayed using chemiluminescence of lucigenin. Results: Incubation of HMC in HG resulted in a 1.6-fold increase in Ang I ( p < 0.05) and a 1.4-fold increase in Ang II levels ( p < 0.05) in cell lysates. These changes were accompanied by a >2-fold increase in O-2(radical anion) accumulation ( p < 0.01), which was inhibited by losartan and irbesartan. Exogenous Ang II increased net O-2(radical anion) accumulation by 2.7- fold ( p < 0.01), which was normalized by losartan and irbesartan. DPI and apocynin blocked the HG and Ang II- induced increases in O-2(radical anion) ( p < 0.01). HG but not exogenous Ang II inhibited total SOD activity by 30%, which was not affected by losartan. Conclusion: High glucose increases O-2(radical anion) accumulation in HMC primarily by increasing its production via the Ang II- NADH/NADPH oxidase system. Copyright (C) 2005 S. Karger AG, Basel.
引用
收藏
页码:E46 / E53
页数:8
相关论文
共 38 条
[1]  
ARAI K, 1987, J BIOL CHEM, V262, P16969
[2]   Angiotensin II induces gene transcription through cell-type-dependent effects on the nuclear factor-κB (NF-κB) transcription factor [J].
Brasier, AR ;
Jamaluddin, M ;
Han, YQ ;
Patterson, C ;
Runge, MS .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2000, 212 (1-2) :155-169
[3]   High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes [J].
Bursell, SE ;
Clermont, AC ;
Aiello, LP ;
Aiello, LM ;
Schlossman, DK ;
Feener, EP ;
Laffel, L ;
King, GL .
DIABETES CARE, 1999, 22 (08) :1245-1251
[4]   Glucose-induced oxidative stress in mesangial cells [J].
Catherwood, MA ;
Powell, LA ;
Anderson, P ;
McMaster, D ;
Sharpe, PC ;
Trimble, ER .
KIDNEY INTERNATIONAL, 2002, 61 (02) :599-608
[5]   Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy [J].
Cooper, ME .
DIABETOLOGIA, 2001, 44 (11) :1957-1972
[6]  
Craven PA, 1997, J AM SOC NEPHROL, V8, P1405
[7]   Overexpression of manganese superoxide dismutase suppresses increases in collagen accumulation induced by culture of mesangial cells in high-media glucose [J].
Craven, PA ;
Phillips, SL ;
Melhem, MF ;
Liachenko, J ;
DeRubertis, FR .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2001, 50 (09) :1043-1048
[8]   Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment [J].
Etoh, T ;
Inoguchi, T ;
Kakimoto, M ;
Sonoda, N ;
Kobayashi, K ;
Kuroda, J ;
Sumimoto, H ;
Nawata, H .
DIABETOLOGIA, 2003, 46 (10) :1428-1437
[9]   Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells [J].
Gorin, Y ;
Ricono, JM ;
Kim, NH ;
Bhandari, B ;
Choudhury, GG ;
Abboud, HE .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2003, 285 (02) :F219-F229
[10]   High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells [J].
Inoguchi, T ;
Li, P ;
Umeda, F ;
Yu, HY ;
Kakimoto, M ;
Imamura, M ;
Aoki, T ;
Etoh, T ;
Hashimoto, T ;
Naruse, M ;
Sano, H ;
Utsumi, H ;
Nawata, H .
DIABETES, 2000, 49 (11) :1939-1945