کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1908607 1046673 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Succinobucol induces apoptosis in vascular smooth muscle cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Succinobucol induces apoptosis in vascular smooth muscle cells
چکیده انگلیسی

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 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.

Figure optionsDownload high-quality image (59 K)Download as PowerPoint slideHighlights
► The succinyl ester of probucol, succinobucol, has failed as an antiatherogenic drug.
► Probucol and succinobucol inhibit vascular smooth muscle cell growth differently.
► Succinobucol induces apoptosis of vascular smooth muscle cells in vitro and in vivo.
► Succinobucol increases mitochondrial oxidants and converts cytochrome c into a peroxidase.
► Succinobucol induces apoptosis dependent on mitochondrial complex II and cytochrome c.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 52, Issue 5, 1 March 2012, Pages 871–879
نویسندگان
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