Faculty Collaboration Database

Activation of heat-shock transcription factor by graded reductions in renal ATP, in vivo, in the rat. J Clin Invest 1994 Oct;94(4):1518-23

Date

10/01/1994

Pubmed ID

7929828

Pubmed Central ID

PMC295298

DOI

10.1172/JCI117492

Scopus ID

2-s2.0-0028031568 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

Renal ischemia results in both a profound fall in cellular ATP and a rapid induction of the 70 kD heat-shock protein family, HSP-70. The present studies examined the relationship between cellular ATP and induction of the stress response in renal cortex. Cellular ATP, continuously monitored by in vivo 31P-NMR spectroscopy, was reduced and maintained at specific, stable levels in renal cortex by partial aortic occlusion for 45 min. Activation of heat-shock transcription factor (HSF) was detected by gel retardation assay and transcription was confirmed by Northern analysis. Activation of HSF was not present, and HSP-70 mRNA induction did not occur when ATP levels were maintained above 60% preocclusion (control) levels. Reduction in cortical ATP levels to 35-50% preocclusion values resulted in HSF activation and low-level expression of inducible HSP-70 mRNA. Cellular ATP of 20-25% control values resulted in a greater level of HSF activation and subsequent HSP-70 mRNA elaboration. HSF was activated at the end of 15 min of total occlusion. The studies indicate that a 50% reduction in cellular ATP in the renal cortex must occur before the stress response is detectable, that reduction of ATP below 25% control levels produces a more vigorous response, and that reperfusion is not required for initiation of a heat-shock response in the kidney. Cellular ATP, or the metabolic consequences associated with ATP depletion, may be a threshold factor for initiation of a stress response in the kidney.

Author List

Van Why SK, Mann AS, Thulin G, Zhu XH, Kashgarian M, Siegel NJ

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

Adenosine Triphosphate
Animals
Constriction, Pathologic
DNA
HSP70 Heat-Shock Proteins
Hydrogen-Ion Concentration
Ischemia
Kidney Cortex
Male
Protein Binding
RNA, Messenger
Rats
Rats, Sprague-Dawley
Transcriptional Activation