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

Sang Kyung Jo, Gang Jee Ko, Chang Su Boo, Won Yong Cho, Hyoung Kyu Kim

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    50 Citations (Scopus)

    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-κB 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-κB 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 κBα (IκBα) with a resultant depletion of cytoplasmic IκBα, indicating that heat preconditioning blocked the activation of the IκB 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-κB-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.

    Original languageEnglish
    Pages (from-to)3082-3092
    Number of pages11
    JournalJournal of the American Society of Nephrology
    Volume17
    Issue number11
    DOIs
    Publication statusPublished - 2006 Nov

    ASJC Scopus subject areas

    • Nephrology

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