Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney

Liang Jun Yan, Namakkal S. Rajasekaran, Srinivasan Sathyanarayanan, Ivor J. Benjamin

Research output: Contribution to journalArticle

40 Citations (Scopus)

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, αB-crystallin (αBC), Hsp70, and Hsp90. Unlike either αBC 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.

Original languageEnglish
Pages (from-to)465-471
Number of pages7
JournalAntioxidants and Redox Signaling
Volume7
Issue number3-4
DOIs
StatePublished - 1 Mar 2005

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Oxidative stress
Heat-Shock Proteins
Oxidation-Reduction
Oxidative Stress
Shock
Kidney
Hot Temperature
Crystallins
Superoxides
Glutathione Disulfide
Transcription
Mitochondrial Membrane Potential
Reperfusion
Membranes
Homeostasis
Down-Regulation
Ischemia
Proteins

Cite this

Yan, Liang Jun ; Rajasekaran, Namakkal S. ; Sathyanarayanan, Srinivasan ; Benjamin, Ivor J. / Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney. In: Antioxidants and Redox Signaling. 2005 ; Vol. 7, No. 3-4. pp. 465-471.
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Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney. / Yan, Liang Jun; Rajasekaran, Namakkal S.; Sathyanarayanan, Srinivasan; Benjamin, Ivor J.

In: Antioxidants and Redox Signaling, Vol. 7, No. 3-4, 01.03.2005, p. 465-471.

Research output: Contribution to journalArticle

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