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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/F1174    most recent 00397.2009v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by George, L. Articles by Asghar, M. PubMed PubMed Citation Articles by George, L. Articles by Asghar, M.

Exercise activates redox-sensitive transcription factors and restores renal D₁ receptor function in old rats

Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, Texas

Submitted July 14, 2009 ; accepted in final form September 15, 2009

We have previously reported that age-associated oxidative stress via protein kinase C (PKC) increases D₁ receptor (D1R) phosphorylation and causes D1R-G protein uncoupling in renal proximal tubules (RPTs) of old Fischer 344 rats. This results in reduced ability of D1R agonist SKF-38393 to inhibit Na⁺-K⁺-ATPase in RPTs of old rats. Here, we studied the effect of treadmill exercise on markers of oxidative stress, PKC, D1R phosphorylation, D1R-G protein coupling, and Na⁺-K⁺-ATPase activity in RPTs of adult and old rats. We found increased levels of malondialdehyde, a marker of oxidative stress, in RPTs of old rats, which decreased during exercise. Nuclear levels of nuclear erythroid-related factor (Nrf)-2 and nuclear factor (NF)-B in RPTs, transcription factors involved in antioxidant enzyme gene transcription, increased in exercised old rats. This was accompanied by an increase in the activity and expression of antioxidant enzymes, superoxide dismutase and heme oxygenase-1. Age-related decrease in the levels of D1R mRNAs and proteins was attenuated during exercise. Furthermore, exercise in old rats decreased PKC activity and D1R phosphorylation and increased SKF-38393-mediated [³⁵S]guanosine 5'-O-(3-thiotriphosphate) binding (an index of D1R-G protein coupling). SKF-38393 also caused inhibition of Na⁺-K⁺-ATPase in these animals. Also, exercise caused a decrease in proteinuria and increase in phosphaturia in old rats. These results suggest beneficial effects of exercise in terms of increasing antioxidant defenses, decreasing oxidative stress, and improving kidney function in general and D1R function in particular in aging. Both Nrf-2 and NF-B seem to play key role in this phenomenon.

exercise; aging; D₁ receptor; nuclear erythroid-related factor-2; nuclear factor-B