Location of α-tocopherol and α-tocotrienol to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts.

Location of α-tocopherol and α-tocotrienol to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts.
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DOI:
10.1186/2193-1801-3-550
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发表时间:
2014
期刊:
影响因子:
--
通讯作者:
Terao J
Terao J
中科院分区:
其他
文献类型:
--
作者:
Nakamura T;Noma A;Terao J

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α-生育酚(α-T)和α-生育三烯酚(α-T3)是公认的亲脂性抗氧化剂。然而,关于它们在异质细胞膜中的位置的知识有限。我们首先通过将α-T和α-T3与培养的小鼠成纤维细胞孵育来研究这些抗氧化剂在异质细胞膜的富含胆固醇的微区(脂筏和小窝)中的分布。α-T和α-T3的细胞摄取水平被调整到相同的顺序,因为在培养细胞中,后者比前者更有效。超离心后,α-T和α-T3被分配到微区组分中。当通过使用甲基-β-环糊精(其从膜中除去胆固醇)进一步证实α-T和α-T3的分布时,α-T被认为分布到微区(约100 μ g/ml)。9%)。相同的处理不影响微区组分中的α-T3含量,表明α-T3不位于这些富含胆固醇的区域中。而α-T和α-T3则能显著抑制UV-A照射下细胞产生过氧化胆固醇。这些结果表明,α-T和α-T3可以作为膜抗氧化剂对抗光照射胆固醇过氧化,而不管它们分布在富含胆固醇的微区。
α-Tocopherol (α-T) and α-tocotrienol (α-T3) are well recognized as lipophilic antioxidants. Nevertheless, there is limited knowledge on their location in heterogeneous cell membranes. We first investigated the distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts. Levels of cellular uptake for α-T and α-T3 were adjusted to the same order, as that of the latter was much more efficient than that of the former in the cultured cells. After ultracentrifugation, α-T and α-T3 were partitioned to the microdomain fractions. When the distribution of α-T and α-T3 was further confirmed by using methyl-β-cyclodextrin (which removes cholesterol from membranes), α-T was suggested to be distributed to the microdomains (approx. 9% of the total uptake). The same treatment did not affect α-T3 content in the microdomain fractions, indicating that α-T3 is not located in these cholesterol-rich domains. However, α-T and α-T3 significantly inhibited the production of peroxidized cholesterol when cells were exposed to ultraviolet-A light. These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.
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