title: p66shc and gender-specific dimorphism in acute renal injury.
abstract: OBJECTIVE
  Acute renal injury (AKI) is more prevalent in males than in females perhaps due to adverse effects of testosterone. The oxidant sensor p66shc is regulated by testosterone, hence may be responsible for the aforementioned gender disparity.
  
  
  METHODS
  Wild-type or p66shc-knockdown renal proximal tubule cells were treated with 400 μM H2O2 in the presence or absence of 100 nM dihydrotestosterone (DHT); the production of reactive oxygen species and cell injury were determined. The impact of DHT on p66shc expression and promoter activity as well as gender-dependent expression of p66shc in the mouse kidney was also determined.
  
  
  RESULTS
  DHT increased H2O2-dependent oxidative stress and injury via p66shc and expression of p66shc via promoter activation. Renal expression of p66shc was higher in male compared to female kidneys.
  
  
  CONCLUSIONS
  Higher sensitivity of the male kidney to AKI may be due to the testosterone-dependent increase in p66shc expression.
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, U.S.A. iarany@umc.edu.
authors.forename: Dustin K
authors.initials: DK
authors.lastname: Reed
authors.forename: Istvan
authors.initials: I
authors.lastname: Arany
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002460:Cell Line; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics* / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D017382:Reactive Oxygen Species; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013196:Dihydrotestosterone; D006861:Hydrogen Peroxide
keywords: Gender; acute kidney injury; androgens; p66shc