Heat preconditioning attenuates renal injury in ischemic ARF in rats: role of heat-shock protein 70 on NF-kappaB-mediated inflammation and on tubular cell injury.

Full Abstract

Although heat preconditioning has been known to be protective in various types of injury, the precise molecular mechanism for this is unclear. Recent observations that indicate that previous heat shock has an anti-inflammatory, antiapoptotic effect led to this investigation of the in vivo effect of heat preconditioning on NF-kappaB activation and inflammation and also on tubular cell injury in ischemic acute renal failure (ARF). Heat preconditioning provided marked functional protection and also reduced histologic evidence of tubular necrosis. Ischemia/reperfusion-induced NF-kappaB activation was suppressed by heat preconditioning with a subsequent decrease in monocyte chemoattractant protein-1 expression and inflammatory cell infiltration. Heat preconditioning also suppressed the accumulation of phosphorylated inhibitory kappaBalpha (IkappaBalpha) with a resultant depletion of cytoplasmic IkappaBalpha, indicating that heat preconditioning blocked the activation of the IkappaB kinase complex. Tubular cell apoptosis, determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, also was decreased by heat preconditioning, and this was accompanied by decreased caspase 3 activation. Among several heat-shock proteins (HSP), HSP-70 was induced primarily by heat preconditioning. Inhibition of HSP-70 by quercetin almost completely reversed the functional protection that was provided by heat preconditioning. These data provide evidence that HSP-70 affords protection via inhibition of NF-kappaB-mediated inflammation and also inhibition of the cell death pathway in ischemic ARF. Further elucidation of the cytoprotective mechanism of stress proteins could facilitate new target or drug development in the treatment of ARF.

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Author information

Author/s: Jo, Sang-Kyung (SK); Ko, Gang Jee (GJ); Boo, Chang Su (CS); Cho, Won Yong (WY); Kim, Hyoung Kyu (HK);

Affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Renal Disease, Korea University Hospital, Seoul, Korea.

Journal and publication information

Publication Type: Journal Article

Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol), published in United States. (Language: eng)

Reference: 2006-Nov; vol 17 (issue 11) : pp 3082-92

Dates: Created 2006/10/27; Completed 2007/06/04; Revised 2008/11/21;

PMID: 17021270, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
HSP70 Heat-Shock Proteins - physiology
Hot Temperature
I-kappa B Proteins - physiology
Inflammation - immunology
Ischemia - complications

Kidney - blood supply; pathology
Kidney Failure, Acute - etiology; immunology; prevention & control
Kidney Tubules - pathology
Male
Rats
Rats, Sprague-Dawley

Associated Chemicals: HSP70 Heat-Shock Proteins (0) ; I-kappa B Proteins (0)

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