| Succinobucol induces apoptosis in vascular smooth muscle cells. | |
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MedLine Citation:
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PMID: 22203369 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Probucol inhibits the proliferation of vascular smooth muscle cells in vitro and in vivo, and the drug reduces intimal hyperplasia and atherosclerosis in animals via induction of heme oxygenase-1 (HO-1). Because the succinyl ester of probucol, succinobucol, recently failed as an antiatherogenic drug in humans, we investigated its effects on smooth muscle cell proliferation. Succinobucol and probucol induced HO-1 and decreased cell proliferation in rat aortic smooth muscle cells. However, whereas inhibition of HO-1 reversed the antiproliferative effects of probucol, this was not observed with succinobucol. Instead, succinobucol but not probucol induced caspase activity and apoptosis, and it increased mitochondrial oxidation of hydroethidine to ethidium, suggestive of the participation of H(2)O(2) and cytochrome c. Also, succinobucol but not probucol converted cytochrome c into a peroxidase in the presence of H(2)O(2), and succinobucol-induced apoptosis was decreased in cells that lacked cytochrome c or a functional mitochondrial complex II. In addition, succinobucol increased apoptosis of vascular smooth muscle cells in vivo after balloon angioplasty-mediated vascular injury. Our results suggest that succinobucol induces apoptosis via a pathway involving mitochondrial complex II, H(2)O(2), and cytochrome c. These unexpected results are discussed in light of the failure of succinobucol as an antiatherogenic drug in humans. |
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Authors:
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Robyn G Midwinter; Ghassan J Maghzal; Joanne M Dennis; Ben J Wu; Hong Cai; Alexandr A Kapralov; Natalia A Belikova; Yulia Y Tyurina; Lan-Feng Dong; Levon Khachigian; Jiri Neuzil; Valerian E Kagan; Roland Stocker |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-21 |
Journal Detail:
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Title: Free radical biology & medicine Volume: - ISSN: 1873-4596 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Centre for Vascular Research, Bosch Institute, and Discipline of Pathology, University of Sydney, Sydney, NSW 2006, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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