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Title 

TNF-α activates death pathway in human aorta smooth muscle cell in the presence of 7-ketocholesterol

Authors 

Hyun Sun LeeJong Sun ChangJin Ah BaekMi Yeon ChungH C LeeB Y RhimD E SokMun Chual RhoYoung Kook KimK Kim

Publisher 

Elsevier

Issue Date 

2005

Citation 

Biochemical and Biophysical Research Communications, vol. 333, no. 4, pp. 1093-1099

Keywords 

7-KetocholesterolatherosclerosisTNF-αvascular smooth muscle cell7 oxocholesterolcell DNAaortaaorta atherosclerosisaorta mediacell death

Abstract 

This study was undertaken to investigate whether a physiologically compatible concentration of 7-ketocholesterol had any effect on human vascular smooth muscle cells (HVSMCs). We found that 7-ketocholesterol changed the viability of human aorta smooth muscle cells (HAoSMC) not by cytotoxicity but by activation of tumor necrosis factor-α receptor (TNFR)-mediated death. Whereas TNF-α did not affect the viability in the presence of 7α-hydroxycholesterol or cholesterol, the cytokine induced HAoSMC death in the presence of 7-ketocholesterol as detected by morphology, viability, and fragmentation of chromosomal DNA. The HAoSMC death was inhibited by a neutralizing anti-TNF receptor 1 (TNFR1) antibody and by the caspase inhibitors of z-VAD and z-DEVD. Activations of caspase-8 and -3 were detected from dying HAoSMCs. 7-Ketocholesterol inhibited translocation of the nuclear factor κB (NF-κB) subunits of p65 and p50 from the cytosol into the nucleus, increase of NF-κB activity, and expression of caspase-8 homolog Fas ligand interleukin-1-converting enzyme inhibitory protein by TNF-α. We also found that X-chromosome-linked inhibitor of apoptosis protein was degraded in dying HAoSMC. The present study proposes that 7-ketocholesterol would contribute to the disappearance of HVSMC in the atherosclerotic lesions by enhancing receptor-mediated death. This is the first report demonstrating induction of TNF-α-mediated death by oxysterol in cells.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2005.05.196

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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