کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1909603 1046732 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Proapoptotic effects of long-chain vitamin E metabolites in HepG2 cells are mediated by oxidative stress
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Proapoptotic effects of long-chain vitamin E metabolites in HepG2 cells are mediated by oxidative stress
چکیده انگلیسی

Although the metabolism of vitamin E has been extensively studied in cell culture, animals, and humans, biochemical analyses of intermediate metabolites are scarce. We here describe the synthesis and proapoptotic properties of long-chain metabolites of α- and δ-tocopherol. Several long-chain vitamin E metabolites, namely 13′-hydroxy- and 13′-carboxychromanols, were synthesized from garcinoic acid, a δ-tocotrienol derivative extracted from the African bitter nut Garcinia kola. Both α- and δ-13′-carboxychromanol induced cell death in HepG2 cells at EC50 of 13.5 and 6.5 μM, respectively. Apoptosis was quantified by annexin V/7-AAD staining and flow cytometry analysis. By immunoblot analyses, we observed activation of both caspase-3 and caspase-9 as well as PARP-1 cleavage. Parameters of mitochondrial dysfunction including reduced mitochondrial membrane potential and increased intracellular and intramitochondrial reactive oxygen species formation were observed after metabolite treatment. Last, long-chain hydroxychromanols were readily metabolized to the corresponding carboxychromanols in HepG2 cells. Taken together, these results indicate that long-chain metabolites may be responsible for antiproliferative properties of vitamin E vitamers.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 49, Issue 8, 1 November 2010, Pages 1315–1322
نویسندگان
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