Reduced tolerance of immature renal tubules to anoxia by HSF-1 decoy. Am J Physiol Renal Physiol 2005 Feb;288(2):F322-6
Date
10/07/2004Pubmed ID
15467004DOI
10.1152/ajprenal.00307.2004Scopus ID
2-s2.0-12144256381 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Immature animals demonstrate an amplified heat shock response following a variety of insults compared with that seen in mature animals (M). The potential role of the heat shock response in modulating immature tolerance to injury was compared between rat pups, 10 postnatal days of age (P10), and M. Baseline levels of the heat shock transcription factor (HSF-1) were substantially elevated in P10 compared with M animals. In uninjured P10 pups, HSF-1 level was comparable to that of M animals subjected to 45 min of ischemia. As anticipated, the integrity of suspensions of tubules exposed to anoxia was preserved in P10 animals (23% LDH release) compared with M (40%), P < 0.01. The effect of targeted inhibition of HSF-1 on tubular integrity was studied using a cyclic oligonucleotide decoy. The HSF-1 decoy increased the severity of anoxic injury in P10 pups to a level comparable with M animals. LDH release was 33% in decoy-treated P10 tubules compared with 40% in M. When P10 tubules were treated with scrambled decoy, resistance to anoxia remained intact (24%). The increased vulnerability of the tubular suspension to injury was specific to the HSF-1 decoy and proportional to the dose of decoy applied. This study demonstrates maturation in the abundance of HSF-1 in the immature rat kidney. The loss of resistance of immature tubules to anoxia with specific inhibition of HSF-1 may be due to its effect on the heat shock response or other signaling pathways of critical pathobiological importance in renal cell injury.
Author List
Sreedharan R, Riordan M, Wang S, Thulin G, Kashgarian M, Siegel NJAuthor
Rajasree Sreedharan MD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptation, PhysiologicalAnimals
Cell Hypoxia
DNA-Binding Proteins
Heat Shock Transcription Factors
Hot Temperature
Kidney Tubules
Oligonucleotides
Rats
Rats, Sprague-Dawley
Signal Transduction
Transcription Factors
Transcription, Genetic