Show simple item record

dc.contributor.authorMidwinter, Robyn G
dc.contributor.authorMaghzal, Ghassan J
dc.contributor.authorDennis, Joanne M
dc.contributor.authorWu, Ben J
dc.contributor.authorCai, Hong
dc.contributor.authorKapralov, Alexandr A
dc.contributor.authorBelikova, Natalia A
dc.contributor.authorTyurina, Yulia Y
dc.contributor.authorDong, Lan-Feng
dc.contributor.authorKhachigian, Levon
dc.contributor.authorNeuzil, Jiri
dc.contributor.authorKagan, Valerian E
dc.contributor.authorStocker, Roland
dc.date.accessioned2017-05-03T12:22:12Z
dc.date.available2017-05-03T12:22:12Z
dc.date.issued2012
dc.date.modified2013-06-20T03:42:51Z
dc.identifier.issn0891-5849
dc.identifier.doi10.1016/j.freeradbiomed.2011.11.029
dc.identifier.urihttp://hdl.handle.net/10072/51665
dc.description.abstractProbucol 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 H2O2 and cytochrome c. Also, succinobucol but not probucol converted cytochrome c into a peroxidase in the presence of H2O2, 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, H2O2, and cytochrome c. These unexpected results are discussed in light of the failure of succinobucol as an antiatherogenic drug in humans.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeNetherlands
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom871
dc.relation.ispartofpageto879
dc.relation.ispartofissue5
dc.relation.ispartofjournalFree Radical Biology & Medicine
dc.relation.ispartofvolume52
dc.rights.retentionY
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.titleSuccinobucol induces apoptosis in vascular smooth muscle cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2012
gro.hasfulltextNo Full Text
gro.griffith.authorNeuzil, Jiri


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record