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类胡萝卜素和视黄醇给药对蒙古沙鼠的蛋白质组反应。

Proteomic responses of carotenoid and retinol administration to Mongolian gerbils.

机构信息

Luxembourg Institute of Health, Population Health Department, 1 A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg.

出版信息

Food Funct. 2018 Jul 17;9(7):3835-3844. doi: 10.1039/c8fo00278a.

Abstract

Various health benefits of carotenoids have been described. However, while human observational studies generally suggest positive health effects, supplementation with relatively high doses of individual carotenoids (supplements) have partly produced adverse effects. In the present study, we investigated the effect of several carotenoids on the proteomic response of male Mongolian gerbils (aged 6 weeks). Five groups of gerbils (n = 6 per group) received either retinol (vitamin A/53 mg per kg bw), all-trans β-carotene (pro-vitamin A/100 mg kg-1), the non-pro vitamin A carotenoid lutein (100 mg kg-1), the acyclic carotenoid lycopene (100 mg kg-1) or vehicle (Cremophor EL), via oral single gavage. Gerbils were 12 h post-prandially sacrificed and blood plasma, liver, and white adipose tissue were collected. For liver and adipose tissue, a 2D-DIGE (difference gel electrophoresis) approach was conducted; for plasma, proteomic analyses were achieved by liquid chromatography-mass spectrometry. Compared to controls (vehicle), various proteins were showing significant abundance variations in plasma (66), liver (29) and adipose tissue (19), especially regarding structure (22), protein metabolism (15) and immune system/inflammation (19) functions, while proteins related to antioxidant effects were generally less abundant, suggesting no in vivo relevance. Surprisingly, a large overlap in protein regulation was found between lycopene and retinol exposure, while other carotenoids, including all-trans β-carotene, did not show this overlap. Mainly retinoid acid receptor co-regulated proteins may mechanistically explain this overlapping regulation. This overlapping regulation may be related to common nuclear hormone receptor mediated signalling, though further studies using synthetic ligands of retinoid receptors targeting protein regulation are needed for confirmation.

摘要

类胡萝卜素具有多种健康益处。然而,虽然人类观察性研究通常表明其具有积极的健康影响,但补充相对高剂量的单一类胡萝卜素(补充剂)部分产生了不良影响。在本研究中,我们研究了几种类胡萝卜素对雄性蒙古沙鼠(6 周龄)蛋白质组响应的影响。将五组沙鼠(每组 6 只)通过口服单次灌胃给予视黄醇(维生素 A/53mg/kg bw)、全反式β-胡萝卜素(维生素 A 前体/100mgkg-1)、非维生素 A 类胡萝卜素叶黄素(100mgkg-1)、非环类胡萝卜素番茄红素(100mgkg-1)或载体(Cremophor EL)。沙鼠在进食后 12 小时被处死,收集血浆、肝脏和白色脂肪组织。对于肝脏和脂肪组织,采用 2D-DIGE(差异凝胶电泳)方法进行;对于血浆,通过液相色谱-质谱法进行蛋白质组学分析。与对照组(载体)相比,血浆(66 个)、肝脏(29 个)和脂肪组织(19 个)中各种蛋白质的丰度变化显著,特别是在结构(22 个)、蛋白质代谢(15 个)和免疫系统/炎症(19 个)功能方面,而与抗氧化作用相关的蛋白质通常较少,表明体内相关性不大。令人惊讶的是,番茄红素和视黄醇暴露之间发现了大量蛋白质调节的重叠,而其他类胡萝卜素,包括全反式β-胡萝卜素,没有表现出这种重叠。主要的视黄酸受体共同调节蛋白可能从机制上解释了这种重叠调节。这种重叠调节可能与常见的核激素受体介导的信号转导有关,但需要使用针对蛋白质调节的视黄酸受体合成配体的进一步研究来证实。

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