Document Detail


Exercise activates redox-sensitive transcription factors and restores renal D1 receptor function in old rats.
MedLine Citation:
PMID:  19759268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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)-kappaB 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-kappaB seem to play key role in this phenomenon.
Authors:
Liza George; Mustafa F Lokhandwala; Mohammad Asghar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-09-16
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  297     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-02     Completed Date:  2009-11-17     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1174-80     Citation Subset:  IM    
Affiliation:
Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
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MeSH Terms
Descriptor/Qualifier:
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
Aging / physiology*
Animals
Dopamine Agonists / pharmacology
GA-Binding Protein Transcription Factor / metabolism
GTP-Binding Proteins / metabolism
Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
Heme Oxygenase-1 / metabolism
Kidney Tubules, Proximal / drug effects,  enzymology,  metabolism
Male
Malondialdehyde / metabolism
NF-kappa B / metabolism
Oxidation-Reduction
Phosphates / urine
Physical Conditioning, Animal / physiology*
Protein Kinase C / metabolism
Proteinuria / metabolism
Rats
Rats, Inbred F344
Receptors, Dopamine D1 / physiology*
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
Superoxide Dismutase / metabolism
Transcription Factors / metabolism*
Grant Support
ID/Acronym/Agency:
AG-029904/AG/NIA NIH HHS; AG-25056/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Agonists; 0/GA-Binding Protein Transcription Factor; 0/Gabpa protein, rat; 0/NF-kappa B; 0/Phosphates; 0/Receptors, Dopamine D1; 0/Transcription Factors; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate); 542-78-9/Malondialdehyde; 67287-49-4/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; EC 1.14.99.3/Heme Oxygenase-1; EC 1.15.1.1/Superoxide Dismutase; EC 2.7.11.13/Protein Kinase C; EC 3.6.1.-/GTP-Binding Proteins; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase
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