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Title: | Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy. | Authors: | Mori T.A.;Tesch G.H.;Atkins R.C.;Croft K.D.;Hertzog P.;Nikolic-Paterson D. ;Kola I.;De Haan J.B.;Stefanovic N.;Scurr L.L. | Institution: | (De Haan, Stefanovic, Hertzog) Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Clayton, Vic., Australia (Nikolic-Paterson, Atkins, Tesch) Department of Nephrology, Monash University, Monash Medical Centre, Clayton, Vic., Australia (Scurr) Department of Gynaecological Oncology, University of Sydney, Westmead Hospital, Sydney, NSW, Australia (Croft, Mori) School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia (Kola) Merck Research Laboratories, Rahway, NJ, United States (Tesch) Dept. of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Vic. 3168, Australia | Issue Date: | 18-Oct-2012 | Copyright year: | 2005 | Publisher: | American Physiological Society (9650 Rockville Pike, Bethesda MD 20814-3991, United States) | Place of publication: | United States | Publication information: | American Journal of Physiology - Renal Physiology. 289 (3 58-3) (pp F544-F551), 2005. Date of Publication: September 2005. | Abstract: | In many diseases, including progressive renal disorders, tissue injury and pathological intracellular signaling events are dependent on oxidative stress. Glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that is highly expressed in the kidney and removes peroxides and peroxynitrite that can cause renal damage. Therefore, we examined whether this abundant renal antioxidant enzyme limits renal damage during the development of type 1 diabetic nephropathy. Wild-type (Gpx1 +/+) and deficient (Gpx1 -/-) mice were made diabetic by intraperitoneal injection of streptozotocin (100 mg/kg) on 2 consecutive days. Diabetic Gpx1 +/+ and -/- mice with equivalent blood glucose levels (23 +/- 4 mM) were selected and examined after 4 mo of diabetes. Compared with normal mice, diabetic Gpx1 +/+ and -/- mice had a two- to threefold increase in urine albumin excretion at 2 and 4 mo of diabetes. At 4 mo, diabetic Gpx1 +/+ and -/- mice had equivalent levels of oxidative renal injury (increased kidney reactive oxygen species, kidney lipid peroxidation, urine isoprostanes, kidney deposition of advanced glycoxidation, and nitrosylation end products) and a similar degree of glomerular damage (hypertrophy, hypercellularity, sclerosis), tubular injury (apoptosis and vimentin expression), and renal fibrosis (myofibroblasts, collagen, TGF-beta excretion). A lack of Gpx1 was not compensated for by increased levels of catalase or other Gpx isoforms in diabetic kidneys. Contrary to expectations, this study showed that the high level of Gpx1 expressed in the kidney is not protective against the development of renal oxidative stress and nephropathy in a model of type 1 diabetes. Copyright © 2005 the American Physiological Society. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1152/ajprenal.00088.2005 | PubMed URL: | 15827346 [http://www.ncbi.nlm.nih.gov/pubmed/?term=15827346] | ISSN: | 0363-6127 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/32314 | Type: | Article | Subjects: | *protein expression *renal protection *streptozocin diabetes tissue injury/di [Diagnosis] collagen glucose *glutathione peroxidase/ec [Endogenous Compound] glutathione peroxidase 1/ec [Endogenous Compound] isoprostane peroxide *streptozocin/ip [Intraperitoneal Drug Administration] *streptozocin/pd [Pharmacology] transforming growth factor beta/ec [Endogenous Compound] unclassified drug vimentin nitrosylation animal cell animal experiment animal model animal tissue apoptosis article controlled study *diabetic nephropathy/co [Complication] *diabetic nephropathy/pc [Prevention] disease course glucose blood level intracellular transport kidney fibrosis/di [Diagnosis] kidney hypertrophy/et [Etiology] kidney injury/et [Etiology] mouse myofibroblast nephrosclerosis/et [Etiology] nonhuman oxidation kinetics oxidative stress priority journal kidney hypertrophy / etiology kidney injury / etiology mouse myofibroblast nephrosclerosis / etiology nitrosylation nonhuman oxidation kinetics oxidative stress priority journal *protein expression animal tissue *streptozocin diabetes tissue injury / diagnosis animal model animal experiment animal cell *renal protection apoptosis article controlled study *diabetic nephropathy / *complication / *prevention disease course glucose blood level intracellular transport kidney fibrosis / diagnosis |
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