Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia - PubMed (original) (raw)

Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia

I J Benjamin et al. J Clin Invest. 1992 May.

Abstract

Expression of major stress proteins is induced rapidly in ischemic tissues, a response that may protect cells from ischemic injury. We have shown previously that transcriptional induction of heat-shock protein 70 by hypoxia results from activation of DNA binding of a preexisting, but inactive, pool of heat shock factor (HSF). To determine the intracellular signals generated in hypoxic or ischemic cells that trigger HSF activation, we examined the effects of glucose deprivation and the metabolic inhibitor rotenone on DNA-binding activity of HSF in cultured C2 myogenic cells grown under normoxic conditions. Whole-cell extracts were examined in gel mobility shift assays using a 39-bp synthetic oligonucleotide containing a consensus heat-shock element as probe. ATP pools were determined by high-pressure liquid chromatography and intracellular pH (pHi) was measured using a fluorescent indicator. Glucose deprivation alone reduced the cellular ATP pool to 50% of control levels but failed to activate HSF. However, 2 x 10(-4) M rotenone induced DNA binding of HSF within 30 min, in association with a fall in ATP to 30% of control levels, and a fall in pHi from 7.3 to 6.9. Maneuvers (sodium propionate and amiloride) that lowered pHi to 6.7 without ATP depletion failed to activate HSF. Conversely, in studies that lowered ATP stores at normal pH (high K+/nigericin) we found induction of HSF-DNA binding activity. Our data indicate that the effects of ATP depletion alone are sufficient to induce the DNA binding of HSF when oxidative metabolism is impaired, and are consistent with a model proposed recently for transcriptional regulation of stress protein genes during ischemia.

PubMed Disclaimer

Cited by

Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle.
Febbraio MA, Steensberg A, Walsh R, Koukoulas I, van Hall G, Saltin B, Pedersen BK. Febbraio MA, et al. J Physiol. 2002 Feb 1;538(Pt 3):911-7. doi: 10.1113/jphysiol.2001.013145. J Physiol. 2002. PMID: 11826174 Free PMC article.
The exercise-induced stress response of skeletal muscle, with specific emphasis on humans.
Morton JP, Kayani AC, McArdle A, Drust B. Morton JP, et al. Sports Med. 2009;39(8):643-62. doi: 10.2165/00007256-200939080-00003. Sports Med. 2009. PMID: 19769414 Review.
Exercise, heat shock proteins and insulin resistance.
Archer AE, Von Schulze AT, Geiger PC. Archer AE, et al. Philos Trans R Soc Lond B Biol Sci. 2018 Jan 19;373(1738):20160529. doi: 10.1098/rstb.2016.0529. Philos Trans R Soc Lond B Biol Sci. 2018. PMID: 29203714 Free PMC article. Review.
Increased immunogenicity is an integral part of the heat shock response following renal ischemia.
Bidmon B, Kratochwill K, Rusai K, Kuster L, Herzog R, Eickelberg O, Aufricht C. Bidmon B, et al. Cell Stress Chaperones. 2012 May;17(3):385-97. doi: 10.1007/s12192-011-0314-2. Epub 2011 Dec 17. Cell Stress Chaperones. 2012. PMID: 22180342 Free PMC article.
Heat shock response is associated with protection against acute interstitial pancreatitis in rats.
Weber H, Wagner AC, Jonas L, Merkord J, Höfken T, Nizze H, Leitzmann P, Göke B, Schuff-Werner P. Weber H, et al. Dig Dis Sci. 2000 Nov;45(11):2252-64. doi: 10.1023/a:1026459001195. Dig Dis Sci. 2000. PMID: 11215749

References

1. Biochemistry. 1979 May 29;18(11):2210-8 - PubMed
1. EMBO J. 1985 Dec 1;4(12):3137-43 - PubMed
1. Mol Biol Med. 1991 Apr;8(2):197-206 - PubMed
1. J Biol Chem. 1991 Aug 5;266(22):14491-6 - PubMed
1. Cell. 1991 May 3;65(3):363-6 - PubMed

Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia - PubMed (original) (raw)