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Title 

Caspase-3-dependent apoptosis in vascular smooth muscle cell by proteasome inhibition

Authors 

S C KimMun Chual RhoHyun Sun LeeYoung Kook KimKoanhoi Kim

Publisher 

Raven Press Publishers

Issue Date 

2003

Citation 

Journal of Cardiovascular Pharmacology, vol. 42, no. 4, pp. 554-560

Keywords 

apoptosisP53proteasomerestenosissmooth muscle cellcaspase 3caspase 8proteasome inhibitorprotein p53animal cell

Abstract 

The effects of a number of substances on neointima formation following angioplasty have been investigated in animal models. It was suggested that delivering of proteasome inhibitor to the site of vascular injury would be a potential therapeutic approach in prevention of vascular restenosis. But the mechanisms underlying biologic activities of proteasome inhibition in vascular smooth muscle cells (VSMCs) are largely unknown. We have investigated effects of proteasome inhibition on VSMCs using proteasome inhibitor MG115. MG115 induced apoptotic death in VSMCs as determined by viability, morphology, and DNA fragmentation. Proteasome inhibition was accompanied by up-regulation of p53, p21, and p27. In contrast, there were no appreciable alterations in the levels of Bcl-2 and Bax. Proteasome inhibition was followed by activation of caspase-3 but not of -8. The induction of apoptosis was suppressed by treatment with a selective inhibitor of the caspase-3 family, z-DEVD-fmk but not by N G-monomethyl-L-arginine. These results indicate that proteasome inhibition induces apoptosis in VSMCs by activation of caspase-3.

ISSN 

0160-2446

Link 

http://dx.doi.org/10.1097/00005344-200310000-00014

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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