title: Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney.
abstract: Increased synthesis of heat shock proteins (Hsps), mainly regulated by heat shock factor 1 (Hsf1), protects the heart against oxidative stress under pathophysiological conditions such as ischemia/reperfusion. To investigate whether Hsps might exert a similar protective effect under physiological conditions in the kidney, we first evaluated the HSF1-dependent expression of several Hsps, including Hsp25, alphaB-crystallin (alphaBC), Hsp70, and Hsp90. Unlike either alphaBC or Hsp70, protein expression of Hsp25 and Hsp90 was decreased 26% and 50%, respectively, in Hsf1 knockout compared with the wild-type mice. The effects of Hsp down-regulation on renal cellular redox status are presently unknown. Indeed, HSF1 deficiency caused a 37% decrease in renal cellular GSH/GSSG ratio, a marker of redox status, and a 40% increase in the rate of mitochondrial superoxide generation in Hsf1 knockout compared with wild-type mice. HSF1 disruption also increased mitochondrial permeability transition pore opening and induced greater mitochondrial membrane potential change (48% increase versus wild type). Thus, the present study demonstrates that Hsf1-dependent transcription of selective Hsps is required for normal renal homeostasis, which protects renal cells against oxidative stress under physiological conditions. The source of mitochondrial superoxide generation is discussed.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yan
authors.forename: Namakkal S
authors.initials: NS
authors.lastname: Rajasekaran
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Sathyanarayanan
authors.forename: Ivor J
authors.initials: IJ
authors.lastname: Benjamin
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism; D018869:Heat-Shock Response; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; D017382:Reactive Oxygen Species; D014157:Transcription Factors