Activation of the heat shock response:: relationship to energy metabolites.: A 31P NMR study in rat hearts

被引:16
作者
Chang, J
Knowlton, AA
Xu, F
Wasser, JS
机构
[1] Baylor Coll Med, Houston, TX 77030 USA
[2] Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA
[3] Vet Affairs Med Ctr, Houston, TX 77030 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2001年 / 280卷 / 01期
关键词
heat shock factor 1; intracellular pH; ATP; free energy of ATP hydrolysis; ischemia; reperfusion; rat heart; cardiac energetics;
D O I
10.1152/ajpheart.2001.280.1.H426
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Heat shock factor (HSF), the transcription factor for the heat shock proteins, is activated by cardiac ischemia, but the mechanism of activation is unknown. Ischemia is accompanied by changes in the energy state and acid-base conditions. We hypothesized that decreased ATP and/or intracellular pH (pH(i)) might activate HSF. To test this hypothesis, we perfused rat hearts within an NMR spectrometer. NMR data showed that after 6.5, 13, and 20 min of ischemia, ATP dropped to 62.7, 23.1, and 6.9% of the control level, and pH(i) was 6.16, 5.94, and 5.79, respectively. Reperfusion after ischemia partially restored ATP levels, and this was associated with greater activation of HSF1. HSF1 was also activated after 6.5 min of ischemia. Activation of HSF1 was less after 13 min of ischemia and barely detectable after 20 min of ischemia. In conclusion, 1) a moderate decrease in intracellular ATP correlates with activation of HSF1 in the heart; and 2) a severe depletion in ATP correlates with an attenuation in HSF1 activation, and the restoration of ATP leads to greater activation of HSF1, suggesting that a critical ATP level is required for activation of HSF1.
引用
收藏
页码:H426 / H433
页数:8
相关论文
共 46 条
[1]   THE HUMAN HEAT-SHOCK PROTEIN HSP70 INTERACTS WITH HSF, THE TRANSCRIPTION FACTOR THAT REGULATES HEAT-SHOCK GENE-EXPRESSION [J].
ABRAVAYA, K ;
MYERS, MP ;
MURPHY, SP ;
MORIMOTO, RI .
GENES & DEVELOPMENT, 1992, 6 (07) :1153-1164
[2]   OXIDATIVE INJURY OF CORONARY VENULAR ENDOTHELIAL-CELLS DEPLETES INTRACELLULAR GLUTATHIONE AND INDUCES HSP-70 MESSENGER-RNA [J].
AUCOIN, MM ;
BARHOUMI, R ;
KOCHEVAR, DT ;
GRANGER, HJ ;
BURGHARDT, RC .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 268 (04) :H1651-H1658
[3]   Model systems for modulating the free energy of ATP hydrolysis in normoxically perfused rat hearts [J].
Balschi, JA ;
Shen, H ;
Madden, MC ;
Hai, JO ;
Bradley, EL ;
Wolkowicz, PE .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1997, 29 (11) :3123-3133
[4]   EXAMINING THE FUNCTION AND REGULATION OF HSP-70 IN CELLS SUBJECTED TO METABOLIC STRESS [J].
BECKMANN, RP ;
LOVETT, M ;
WELCH, WJ .
JOURNAL OF CELL BIOLOGY, 1992, 117 (06) :1137-1150
[5]   INTERACTION OF HSP-70 WITH NEWLY SYNTHESIZED PROTEINS - IMPLICATIONS FOR PROTEIN FOLDING AND ASSEMBLY [J].
BECKMANN, RP ;
MIZZEN, LA ;
WELCH, WJ .
SCIENCE, 1990, 248 (4957) :850-854
[6]   Stress (heat shock) proteins - Molecular chaperones in cardiovascular biology and disease [J].
Benjamin, IJ ;
McMillan, DR .
CIRCULATION RESEARCH, 1998, 83 (02) :117-132
[7]   INDUCTION OF STRESS PROTEINS IN CULTURED MYOGENIC CELLS - MOLECULAR SIGNALS FOR THE ACTIVATION OF HEAT-SHOCK TRANSCRIPTION FACTOR DURING ISCHEMIA [J].
BENJAMIN, IJ ;
HORIE, S ;
GREENBERG, ML ;
ALPERN, RJ ;
WILLIAMS, RS .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (05) :1685-1689
[8]   ACTIVATION OF THE HEAT-SHOCK TRANSCRIPTION FACTOR BY HYPOXIA IN MAMMALIAN-CELLS [J].
BENJAMIN, IJ ;
KROGER, B ;
WILLIAMS, RS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (16) :6263-6267
[9]   P-31 NMR MEASUREMENTS OF MYOCARDIAL PH INVIVO [J].
BRINDLE, KM ;
RAJAGOPALAN, B ;
WILLIAMS, DS ;
DETRE, JA ;
SIMPLACEANU, E ;
HO, C ;
RADDA, GK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 151 (01) :70-77
[10]  
BRUCE JL, 1993, CANCER RES, V53, P12