HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/F700    most recent 90548.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ghosh, S. Articles by Laher, I. Search for Related Content PubMed PubMed Citation Articles by Ghosh, S. Articles by Laher, I.

Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice

¹Department of Pathology and Laboratory Medicine, ³Department of Anaesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, ⁴James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; ²Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran; ⁵Cancer Genomics Facility of Kimmel Cancer Center at Thomas Jefferson University, Philadelphia; ⁶Department of Anatomy, Cell Biology, and Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania; ⁷Department of Pathology, School of Medicine, University of California, La Jolla; ⁸Division of Nephrology and Hypertension, Department of Medicine, University of California/Veterans Affairs Health System, La Jolla; and ⁹Translational Research in Kidney Disease, Department of Medicine, University of California, La Jolla, California

Submitted 16 September 2008 ; accepted in final form 8 January 2009

Diabetic nephropathy, the leading cause of end-stage renal disease, is characterized by a proapoptotic and prooxidative environment. The mechanisms by which lifestyle interventions, such as exercise, benefit diabetic nephropathy are unknown. We hypothesized that exercise inhibits early diabetic nephropathy via attenuation of the mitochondrial apoptotic pathway and oxidative damage. Type 2 diabetic db/db and normoglycemic wild-type mice were exercised for an hour everyday at a moderate intensity for 7 wk, following which renal function, morphology, apoptotic signaling, and oxidative stress were evaluated. Exercise reduced body weight, albuminuria, and pathological glomerular expansion in db/db mice independent of hyperglycemic status. Changes in renal morphology were also related to reduced caspase-3 (main effector caspase in renal apoptosis), caspase-8 (main initiator caspase of the "extrinsic" pathway) activities, and TNF- expression. A role for the mitochondrial apoptotic pathway was unlikely as both caspase-9 activity (initiator caspase of this pathway) and expression of regulatory proteins such as Bax and Bcl-2 were unchanged. Kidneys from db/db mice also produced higher levels of superoxides and had greater oxidative damage concurrent with downregulation of superoxide dismutase (SOD) 1 and 3. Interestingly, although exercise also increased superoxides, there was also upregulation of multiple SODs that likely inhibited lipid (hydroperoxides) and protein (carbonyls and nitrotyrosine) oxidation in db/db kidneys. In conclusion, exercise can inhibit progression of early diabetic nephropathy independent of hyperglycemia. Reductions in caspase-3 and caspase-8 activities, with parallel improvements in SOD expression and reduced oxidative damage, could underlie the beneficial effects of exercise in diabetic kidney disease.

kidney; superoxide dismutase