Astaxanthin analogs, adonixanthin and lycopene, activate Nrf2 to prevent light-induced photoreceptor degeneration
Astaxanthin analogs, adonixanthin and lycopene, activate Nrf2 to prevent light-induced photoreceptor degeneration
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DOI：
10.1016/j.jphs.2017.05.011
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发表时间：
2017-07-01
影响因子：
3.5
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
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作者：
Inoue, Yuki;Shimazawa, Masamitsu;Hara, Hideaki
类胡萝卜素，特别是虾青素，具有强大的抗氧化能力。虾青素还可诱导nf - e2相关因子2 (Nrf2)， Nrf2在抗氧化反应中起主要调节作用。然而，人们对虾青素的副产物类胡萝卜素是否激活Nrf2知之甚少。为此，我们通过定量逆转录聚合酶链反应（qRT-PCR）筛选了8种虾青素类似物，以激活小鼠光感受器细胞系661 W中的Nrf2。此外，我们还监测了661个虾青素类似物预处理或仅虾青素类似物预处理6小时后暴露于光下的W细胞的细胞死亡情况。此外，我们还量化了活性氧（ROS）的产生。核染色法测定光照后细胞死亡情况。经qRT-PCR检测，Nrf2调控基因Ho-1、Nqo-1和Gclm以及Nrf2在暴露虾青素、胆青素、紫紫酮和番茄红素的661 W细胞中表达上调。此外，虾青素、阿多黄质、紫锥烯酮、β -胡萝卜素、阿多红素和番茄红素，而不是角黄素，抑制ROS的产生并保护细胞免受光诱导的损伤。此外，仅在光照射前用阿多黄质或番茄红素预处理可防止光诱导的细胞损伤，而Nrf2沉默则取消了这些作用。这些发现表明，更有效的虾青素类似物，如阿多黄质和番茄红素，不仅通过抗氧化反应，还通过Nrf2激活来保护光诱导的细胞损伤。(C) 2017年作者。由Elsevier B.V.代表日本药理学会制作和主办。
Carotenoids, in particular astaxanthin, possess potent antioxidant capabilities. Astaxanthin also induces NF-E2-related factor 2 (Nrf2), which plays a major regulatory role in the antioxidative response. However, little is known whether the carotenoid, by-products of astaxanthin, activate Nrf2. Toward this end, we screened eight astaxanthin analogs for Nrf2 activation in murine photoreceptor cell line, 661 W, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, we monitored cell death in 661 W cells pretreated with astaxanthin analogs or only pretreated for 6 h with astaxanthin analogs and then exposed to light. Furthermore, we quantified the reactive oxygen species (ROS) production. Cell death was quantified after light exposure by nuclear staining. Nrf2-controlled genes Ho-1, Nqo-1, and Gclm by qRT-PCR and Nrf2 in the nucleus were upregulated in 661 W cells exposed astaxanthin, adonixanthin, echinenone, and lycopene. Moreover, astaxanthin, adonixanthin, echinenone, beta-carotene, adonirubin, and lycopene, but not canthaxanthin, suppressed ROS production and protected cells against light-induced damage. Moreover, pretreatment with adonixanthin or lycopene only before light exposure protected against light-induced cell damage and Nrf2 silencing canceled these effects. These findings indicate that the more potent astaxanthin analogs, adonixanthin and lycopene, protect against light-induced cell damage through not only an anti-oxidative response but also through Nrf2 activation. (C) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.