YC-1 induces heat shock protein 70 expression and prevents oxidized LDL-mediated apoptosis in vascular smooth muscle cells

Yi Nan Liu, Shiow Lin Pan, Chieh Yu Peng, Der Yi Huang, Jih Hwa Guh, Sheng Chu Kuo, Fang Yu Lee, Che Ming Teng

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Heat shock protein 70 (hsp70) functioning as molecular chaperon in physiological conditions is induced under stress environment, which affords a defensive mechanism for cells to escape cellular damage. Hence, it is a critical issue to develop a nontoxic hsp70-inducing compound against cellular death. The present study was conducted to evaluate whether 3-(5′-hydroxymethyl- 2′-furyl)-1-benzyl-indazol (YC-1) can effectively induce hsp70 expression and protect vascular smooth muscle cells (VSMCs) against oxidized low-density lipoprotein-induced cytotoxicity. We showed that YC-1 enhanced hsp70 expression in VSMCs through a concentration- and time-dependent manner with maximum expression at 18 and 24 h without involving the cyclic guanosine monophosphate and reactive oxygen species signal in the pathway. Furthermore, we did not observe significant cytotoxicity after YC-1 treatment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactic dehydrogenase, and fluorescence activating cell sorting scan assays. We demonstrated that the nuclear level of heat shock transcription factor 1 increased at 2 h after YC-1 treatment, and hsp70 expression was directed by the up-regulation of hsp70 mRNA, which peaked at 6 h and was followed by a decline. Hence, translocation of heat shock transcription factor 1 and increased level of hsp70 mRNA would account for Hsp70 expression. Finally, we found that YC-1 protects VSMCs from oxidized low-density lipoprotein-inducing apoptosis. According to our observations, YC-1 would be an effectively pharmacological hsp70 inducer that can be used as a cytoprotective agent in vascular diseases.

Original languageEnglish
Pages (from-to)274-279
Number of pages6
JournalShock
Volume30
Issue number3
DOIs
Publication statusPublished - Sep 2008
Externally publishedYes

Keywords

  • Heat shock protein 70
  • Heat shock transcription factor 1
  • YC-1

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

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