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

• Published in: Shock (Augusta, Ga.) Ga.), 2008-09, Vol.30 (3), p.274-279
• Main Authors: Liu, Yi-Nan, Pan, Shiow-Lin, Peng, Chieh-Yu, Huang, Der-Yi, Guh, Jih-Hwa, Kuo, Sheng-Chu, Lee, Fang-Yu, Teng, Che-Ming
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Cell Nucleus - metabolism; DNA-Binding Proteins - biosynthesis; Enzyme Activators - pharmacology; Flow Cytometry; Gene Expression Regulation; Heat Shock Transcription Factors; HSP70 Heat-Shock Proteins - biosynthesis; HSP70 Heat-Shock Proteins - metabolism; Indazoles - pharmacology; Lipoproteins, LDL - metabolism; Male; Models, Biological; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - pathology; Rats; Rats, Wistar; Transcription Factors - biosynthesis
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/shk.0b013e318162c63a

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.