Heat shock factor 1 induces crystallin-αB to protect against cisplatin nephrotoxicity

Qiang Lou, Yanzhong Hu, Yuanfang Ma, Zheng Dong

Research output: Contribution to journalArticle

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Abstract

Cisplatin, a wildly used chemotherapy drug, induces nephrotoxicity that is characterized by renal tubular cell apoptosis. In response to toxicity, tubular cells can activate cytoprotective mechanisms, such as the heat shock response. However, the role and regulation of the heat shock response in cisplatin-induced nephrotoxicity remain largely unclear. In the present study, we demonstrated the induction of heat shock factor (Hsf)1 and the small heat shock protein crystallin-αB (CryAB) during cisplatin nephrotoxicity in mice. Consistently, cisplatin induced Hsf1 and CryAB in a cultured renal proximal tubular cells (RPTCs). RPTCs underwent apoptosis during cisplatin treatment, which was increased when Hsf1 was knocked down. Transfection or restoration of Hsf1 into Hsf1 knockdown cells suppressed cisplatin-induced apoptosis, further supporting a cytoprotective role of Hsf1 and its associated heat shock response. Moreover, Hsf1 knockdown increased Bax translocation to mitochondria and cytochrome c release into the cytosol. In RPTCs, Hsf1 knockdown led to a specific downregulation of CryAB. Transfection of CryAB into Hsf1 knockdown cells diminished their sensitivity to cisplatin-induced apoptosis, suggesting that CryAB may be a key mediator of the cytoprotective effect of Hsf1. Taken together, these results demonstrate a heat shock response in cisplatin nephrotoxicity that is mediated by Hsf1 and CryAB to protect tubular cells against apoptosis.

Original languageEnglish (US)
Pages (from-to)F94-F102
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Crystallins
Cisplatin
Shock
Hot Temperature
Heat-Shock Response
Apoptosis
Kidney
Transfection
Small Heat-Shock Proteins
Cytochromes c
Cytosol
Mitochondria
Down-Regulation
Drug Therapy

Keywords

  • Cisplatin nephrotoxicity
  • Crystallin-αB
  • Heat shock factor 1
  • Heat shock response
  • Renal tubular cell

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Heat shock factor 1 induces crystallin-αB to protect against cisplatin nephrotoxicity. / Lou, Qiang; Hu, Yanzhong; Ma, Yuanfang; Dong, Zheng.

In: American Journal of Physiology - Renal Physiology, Vol. 311, No. 1, 01.07.2016, p. F94-F102.

Research output: Contribution to journalArticle

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