TY - JOUR
T1 - Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney
AU - Yan, Liang Jun
AU - Rajasekaran, Namakkal S.
AU - Sathyanarayanan, Srinivasan
AU - Benjamin, Ivor J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=14044270113&partnerID=8YFLogxK
U2 - 10.1089/ars.2005.7.465
DO - 10.1089/ars.2005.7.465
M3 - Article
C2 - 15706094
AN - SCOPUS:14044270113
SN - 1523-0864
VL - 7
SP - 465
EP - 471
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 3-4
ER -