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

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TNF-α activates death pathway in human aorta smooth muscle cell in the presence of 7-ketocholesterol
Hyun Sun Lee; Jong Sun Chang; Jin Ah Baek; Mi Yeon Chung; H C Lee; B Y Rhim; D E Sok; Mun Chual Rho; Young Kook Kim; K Kim
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 333, no. 4, pp. 1093-1099
Publication Year
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.
7-KetocholesterolatherosclerosisTNF-αvascular smooth muscle cell
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Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
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