Differential Mechanisms of Action and Efficacy of Vitamin E Components in Antioxidant Cytoprotection of Human Retinal Pigment Epithelium.
Differential Mechanisms of Action and Efficacy of Vitamin E Components in Antioxidant Cytoprotection of Human Retinal Pigment Epithelium.
复制标题
DOI：
10.3389/fphar.2021.798938
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Koulen P
中科院分区：
文献类型：
--
作者：
Duncan RS;Hurtado DT;Hall CW;Koulen P
本研究的目的是确定不同的维生素E组分在保护视网膜色素上皮细胞（RPE）免受氧化损伤方面是否表现出相似的功效和作用机制。我们假设α-生育酚（αT）在维生素E组分中是独特的，其细胞保护作用机制是对抗RPE细胞中的氧化应激，并且其需要蛋白质合成以获得最佳抗氧化作用。我们使用细胞活力测定、DNA和肌动蛋白的荧光化学标记、抗氧化蛋白Nrf 2和Sod 2以及紧密连接蛋白ZO-1的免疫标记以及共聚焦显微镜来确定αT和γT对永生化人RPE细胞（hTERT-RPE）中氧化应激的影响。使用四种主要的维生素E组分，αT，γT，δ-生育酚（δT）和α-生育三烯酚（αTr），我们确定，当以等摩尔浓度使用时，它们表现出与αT相似但不相同的抗氧化活性。此外，我们确定了RPE细胞暴露于α-生育酚的时间对于其保护免受氧化损伤的能力至关重要。最后，我们确定αT（而不是γT）部分需要在24小时内和暴露于tBHP之前合成新蛋白质以获得最佳细胞保护。我们的结论是，与γT和δT不同，αT似乎是独特的，它需要运输和/或信号，它是一种有效的抗氧化剂。因此，应更加关注哪些维生素E成分用于抗氧化干预。
The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique among vitamin E components in its cytoprotective mechanism of action against oxidative stress in RPE cells and that it requires protein synthesis for optimal antioxidant effect. We used cell viability assays, fluorescent chemical labeling of DNA and actin and immuno-labeling of the antioxidant proteins Nrf2 and Sod2 and of the tight junction protein, ZO-1, and confocal microscopy to determine the effects of αT and γT against oxidative stress in immortalized human RPE cells (hTERT-RPE). Using the four main vitamin E components, αT, γT, δ-tocopherol (δT) and α-tocotrienol (αTr), we ascertained that they exhibit similar, but not identical, antioxidant activity as αT when used at equimolar concentrations. In addition, we determined that the exposure time of RPE cells to α-tocopherol is critical for its ability to protect against oxidative damage. Lastly, we determined that αT, but not γT, partially requires the synthesis of new proteins within a 24-h period and prior to exposure to tBHP for optimal cytoprotection. We conclude that, unlike γT and δT, αT appears to be unique in its requirement for transport and/or signaling for it to be an effective antioxidant. As a result, more focus should be paid to which vitamin E components are used for antioxidant interventions.
登录
查看更多内容
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
--
作者：
Kassoff, A;Kassoff, J;Chew, EY
通讯作者：
Chew, EY
影响因子：
13.7
作者：
Chakravarthy, U.;Augood, C.;Fletcher, A. E.
通讯作者：
Fletcher, A. E.
影响因子：
3.5
作者：
Hosomi, A;Arita, M;Inoue, K
通讯作者：
Inoue, K
影响因子：
4
作者：
Jamro, Erica L.;Bloom, Michael S.;Fujimoto, Victor Y.
通讯作者：
Fujimoto, Victor Y.