Glucose-6-phosphate dehydrogenase-deficient mice have increased renal oxidative stress and increased albuminuria.
Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway and the principal source of NADPH, a major cellular reductant, and is central to cell survival. Our previous work showed that diabetes and increased aldosterone are acquired forms of G6PD deficiency, leading to decreased G6PD activity and NADPH levels and damage to kidney tissue and endothelial cells. In this study, G6PD-deficient mice were studied to test the hypothesis that decreased G6PD activity per se can cause changes similar to those seen in the acquired conditions of G6PD deficiency. Results show that as compared with control mice, G6PD-deficient mice had increased oxidative stress, as manifested by decreased NADPH levels and decreased GSH levels, and increased markers of lipid peroxidation. G6PD-deficient mice had increased protein kinase C activity, increased nuclear factor-kappaB activity, and increased urinary albumin levels, all of which is similar to changes seen in diabetic mice. Changes persisted as the mice aged, as old G6PD-deficient mice (17-20 mo) had higher urine albumin levels and also had evidence for increased apoptosis in the renal cortex. These results show that decreased G6PD activity per se is sufficient to cause changes similar to those seen in diabetic mice.
Xu
Yizhen
Y
Renal Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
Zhang
Zhaoyun
Z
Hu
Ji
J
Stillman
Isaac E
IE
Leopold
Jane A
JA
Handy
Diane E
DE
Loscalzo
Joseph
J
Stanton
Robert C
RC
D000375:Aging / Q000502:physiology; D000419:Albuminuria / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000097:blood / Q000378:metabolism*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D020672:I-kappa B Proteins / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology; D008297:Male; D051379:Mice; D009249:NADP / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D000975:Antioxidants; D020672:I-kappa B Proteins; D016328:NF-kappa B; D051028:bcl-2-Associated X Protein; D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D011493:Protein Kinase C; D005978:Glutathione