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Exercise as an antioxidant decreases age‐associated oxidative stress and protein kinase C activity and restores D1 receptor function in renal proximal tubules of old rats
Author(s) -
George Liza E.,
Lokhandwala Mustafa F.,
Asghar Mohammad
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb152
Subject(s) - endocrinology , medicine , oxidative stress , protein kinase c , malondialdehyde , superoxide dismutase , chemistry , antioxidant , receptor , agonist , biology , kinase , biochemistry
Age‐associated oxidative stress (OS) via protein kinase C (PKC) activation causes D1 receptor G‐protein (D1R/G) uncoupling resulting in inability of dopamine to inhibit Na,K‐ATPase (NKA) in proximal tubules (PT) of old compared to adult Fisher 344 rats. Our hypothesis is that 3‐month exercise in old rats reduces OS, normalizes PKC activity and restores D1R/G coupling in PT. Biochemical, pharmacological and immunological studies were undertaken in PT of exercised and sedentary adult and old rats. We found that OS markers malondialdehyde and protein carbonyls in PT decreased in exercised rats. This was accompanied by an increase in antioxidant enzymes (AEs), superoxide dismutase and hemeoxygenase. Moreover, Nrf‐2 and NFκB in PT nuclei, transcription factors involved in AEs genes transcription, increased in exercised rats. Interestingly, PKC activity decreased and D1R agonist SKF38393‐ mediated 35 S‐GTPγS binding and inhibition of NKA increased in PT of exercised rats. Also, D1R numbers and D1R proteins increased in PT of exercised rats. Furthermore, exercise decreased proteinuria and increased phosphaturia in rats. These results suggest beneficial effects of exercise in increasing anti‐oxidant defenses and improving kidney function in general and D1R function in particular in aging. Both Nrf‐2 and NFκB seem to be involved in this phenomenon. [Funding: NIH/NIA AG25056, AG29904].