Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina
Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina
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DOI：
10.1016/j.biopha.2022.113117
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发表时间：
2022-05-30
影响因子：
7.5
通讯作者：
Song, Weitao
中科院分区：
文献类型：
--
作者：
Dai, Shirui;Wang, Chao;Song, Weitao
谷氨酸兴奋性毒性可引起细胞损伤和凋亡，在多种视网膜疾病中发挥重要作用。叔丁基对苯二酚（tBHQ）是一种经批准的食品级酚类抗氧化剂，在多种细胞和组织中具有抗氧化活性。本研究通过体外细胞实验观察了tBHQ对多巴胺能受体激动剂诱导的视网膜损伤的保护作用，并探讨了其可能的作用机制。结果表明，tBHQ对NMDA诱导的小鼠视网膜兴奋性毒性和谷氨酸诱导的大鼠视网膜前体细胞（R28细胞）兴奋性毒性具有保护作用。tBHQ逆转谷氨酸诱导的细胞凋亡、细胞内活性氧的产生和线粒体膜电位的降低。Western blot分析显示，tBHQ可增加谷氨酸处理的细胞中caspase-3、Bcl-2、AIF前体、CAT、SOD 2、Nrf 2、NQO 1、HO-1和NF-κ B的表达，降低AIF裂解产物的表达。此外，我们发现tBHQ激活Muller神经胶质细胞。基于这些结果，tBHQ可能具有抗氧化和抗凋亡特性，从而作为一个潜在的视网膜保护剂。其抗氧化应激作用与上调Nrf 2表达有关，抗凋亡作用与上调Bcl-2表达和抑制凋亡相关蛋白依赖性凋亡有关。
Glutamate excitotoxicity can cause cell damage and apoptosis and play an important role in a variety of retinal diseases. Tertiary-butylhydroquinone (tBHQ) is an approved food-grade phenolic antioxidant with antioxidant activity in a variety of cells and tissues. We observed the protective effect of tBHQ on glutamatergic agonistinduced retina and explored its possible mechanism of action through in vitro cell experiments. The results showed that tBHQ had protective effects on NMDA-induced mouse retinal excitotoxicity and glutamate-induced excitotoxicity in rat retinal precursor cells (R28 cells). tBHQ reversed glutamate-induced apoptosis, production of intracellular reactive oxygen species, and reduction of mitochondrial membrane potential. Western blot analysis showed that tBHQ could increase the expression of procaspase-3, Bcl-2, AIF precursor, CAT, SOD2, Nrf2, NQO1, HO-1 and NF-kappa B in glutamate-treated cells, and decrease the expression of AIF cleavage products. Furthermore, we discovered that tBHQ activated muller glial cells. Based on these results, tBHQ may have antioxidant and antiapoptotic properties, thus serving as a potential retinal protective agent. Its anti-oxidative stress effect was attributed to up-regulation of Nrf2, and its anti-apoptotic effect was related to its up-regulation of Bcl-2 expression and inhibition of mitochondria-dependent apoptosis.