YC-1 induces heat shock protein 70 expression and prevents oxidized LDL-mediated apoptosis in vascular smooth muscle cells.
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.
Liu
Yi-Nan
YN
Phamacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
Pan
Shiow-Lin
SL
Peng
Chieh-Yu
CY
Huang
Der-Yi
DY
Guh
Jih-Hwa
JH
Kuo
Sheng-Chu
SC
Lee
Fang-Yu
FY
Teng
Che-Ming
CM
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D020536:Enzyme Activators / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D007191:Indazoles / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D020536:Enzyme Activators; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D007191:Indazoles; D008077:Lipoproteins, LDL; D014157:Transcription Factors; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole