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Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney. Antioxid Redox Signal 2005 Mar-Apr;7(3-4):465-71

Date

02/12/2005

Pubmed ID

15706094

DOI

10.1089/ars.2005.7.465

Scopus ID

2-s2.0-14044270113   41 Citations

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.

Author List

Yan LJ, Rajasekaran NS, Sathyanarayanan S, Benjamin IJ

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
DNA-Binding Proteins
Heat Shock Transcription Factors
Heat-Shock Proteins
Heat-Shock Response
Kidney
Mice
Mice, Knockout
Mitochondria
Oxidation-Reduction
Oxidative Stress
Reactive Oxygen Species
Transcription Factors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a