Mouse heat shock transcription factor 1 deficiency alters cardiac redox homeostasis and increases mitochondrial oxidative damage. EMBO J 2002 Oct 01;21(19):5164-72
Date
10/03/2002Pubmed ID
12356732Pubmed Central ID
PMC129050DOI
10.1093/emboj/cdf528Scopus ID
2-s2.0-0036790590 (requires institutional sign-in at Scopus site) 204 CitationsAbstract
In this study, using heat shock factor 1 (Hsf1) knockout mice as a model, we tested the hypothesis that HSF1-dependent regulation of heat shock proteins (Hsps) is required to maintain redox state and attenuate oxidative damage in the normal heart. Here we report that, in mice, HSF1 deficiency reduces cardiac expression of Hsp25, alphaB-crystallin and Hsp70, but not Hsp60 and Hsp90. Consistent with the downregulation of Hsp25, for example, a significantly lower glutathione (GSH)/glutathione disulfate (GSSG) ratio was associated with the decreased activity, but not protein content, of glucose 6-phosphate dehydrogenase. Con sequently, superoxide was generated at a higher rate, and several mitochondrial proteins, including adenine nucleotide translocase 1 (ANT1), were more oxidized by HSF1 deficiency in vivo. Oxidative damage to ANT1 protein, a structural component of the mitochondrial permeability transition pore (MPTP), decreases its catalytic activity and increases MPTP opening, respectively. Taken together, our results indicate for the first time that constitutive expression of HSP chaperones requires HSF1 activity, and that such HSF1-dependent requirements are directly and functionally linked to maintain redox homeostasis and antioxidative defenses at normal (37 degrees C) temperature.
Author List
Yan LJ, Christians ES, Liu L, Xiao X, Sohal RS, Benjamin IJAuthor
Ivor J. Benjamin MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDNA-Binding Proteins
Gene Expression Regulation
Glucosephosphate Dehydrogenase
Glutathione
Glutathione Disulfide
Heart
Heat Shock Transcription Factors
Heat-Shock Proteins
Homeostasis
Mice
Mice, Knockout
Mitochondria, Heart
Oxidation-Reduction
Oxidative Stress
Submitochondrial Particles
Superoxides
Transcription Factors
