Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2.
Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2.
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DOI：
10.3390/antiox10030413
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发表时间：
2021-03-09
期刊：
影响因子：
--
通讯作者：
Poliakov E
中科院分区：
文献类型：
--
作者：
Uppal S;Dergunov SA;Zhang W;Gentleman S;Redmond TM;Pinkhassik E;Poliakov E
大量的工作已经记录了叶黄素（叶黄素和玉米黄质）在人类健康中的抗氧化作用，特别是它们如何在人类视觉中提供光保护。最近，有证据表明叶黄素/叶黄素裂解产物对抗氧化反应的转录调节，类似于β-胡萝卜素裂解产物在调节视黄酸受体中的作用。补充叶黄素还为预防年龄相关性黄斑变性（AMD）和减轻阿尔茨海默病症状提供了额外的益处。哺乳动物β-胡萝卜素加氧酶2（BCO 2）在体外不对称切割叶黄素和β-胡萝卜素。我们最近证明，小鼠BCO 2（mBCO 2）是一种功能性棕榈酰化酶，当细胞用β-胡萝卜素处理时，它会失去棕榈酰化。小鼠酶是研究哺乳动物BCO 2最简单的模型，因为它只有一种同种型，不像人类BCO 2有几种主要的同种型，具有各种特性。在这里，我们使用相同的酰基RAC方法和共聚焦显微镜来阐明棕榈酰化和本地化的mBCO 2的叶黄素存在下的状态。我们创建了基于大单层囊泡的纳米载体，用于将叶黄素成功递送到细胞中。我们在这里证明，在处理低微摩尔浓度的叶黄素，（0.15 µM），mBCO 2被脱棕榈酰化，并显示部分核定位（38.00 ± 0.04%），当用玉米黄质处理时（0.45 µM）和紫黄质（0.6 µM）诱导线粒体脱棕榈酰化和蛋白质易位的程度较低（分别为20.00 ± 0.01%和35.00 ± 0.02%）。mBCO 2对各种叶黄素的行为的这种差异及其在各种叶黄素存在下易位到细胞核中表明了叶黄素/叶黄素裂解产物转运到细胞核以影响转录调控的可能机制。
An extensive body of work has documented the antioxidant role of xanthophylls (lutein and zeaxanthin) in human health and specifically how they provide photoprotection in human vision. More recently, evidence is emerging for the transcriptional regulation of antioxidant response by lutein/lutein cleavage products, similar to the role of β-carotene cleavage products in the modulation of retinoic acid receptors. Supplementation with xanthophylls also provides additional benefits for the prevention of age-related macular degeneration (AMD) and attenuation of Alzheimer’s disease symptoms. Mammalian β-carotene oxygenase 2 (BCO2) asymmetrically cleaves xanthophylls as well as β-carotene in vitro. We recently demonstrated that mouse BCO2 (mBCO2) is a functionally palmitoylated enzyme and that it loses palmitoylation when cells are treated with β-carotene. The mouse enzyme is the easiest model to study mammalian BCO2 because it has only one isoform, unlike human BCO2 with several major isoforms with various properties. Here, we used the same acyl-RAC methodology and confocal microscopy to elucidate palmitoylation and localization status of mBCO2 in the presence of xanthophylls. We created large unilamellar vesicle-based nanocarriers for the successful delivery of xanthophylls into cells. We demonstrate here that, upon treatment with low micromolar concentration of lutein (0.15 µM), mBCO2 is depalmitoylated and shows partial nuclear localization (38.00 ± 0.04%), while treatment with zeaxanthin (0.45 µM) and violaxanthin (0.6 µM) induces depalmitoylation and protein translocation from mitochondria to a lesser degree (20.00 ± 0.01% and 35.00 ± 0.02%, respectively). Such a difference in the behavior of mBCO2 toward various xanthophylls and its translocation into the nucleus in the presence of various xanthophylls suggests a possible mechanism for transport of lutein/lutein cleavage products to the nucleus to affect transcriptional regulation.
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