ESeroS-GS Protects Neuronal Cells from Oxidative Stress by Stabilizing Lysosomes.
ESeroS-GS Protects Neuronal Cells from Oxidative Stress by Stabilizing Lysosomes.
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ESeroS-GS 通过稳定溶酶体保护神经细胞免受氧化应激
DOI：
10.3390/molecules21060637
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发表时间：
2016-05-25
期刊：
影响因子：
--
通讯作者：
Wei T
中科院分区：
文献类型：
--
作者：
Yang N;Chen Q;He X;Zhao X;Wei T
γ-l-glutamyl-S-[2-[[[3，4-dihydro-2，5，7，8-tetramethyl-2-(4，8，12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-l-cysteinylglycine钠盐(ESeroS-GS)是α-生育酚(维生素E)的水溶性衍生物。我们先前报道，ESeroS-GS可以作为抗炎剂，并可以诱导乳腺癌细胞死亡。然而，ESeroS-GS的潜在抗氧化能力仍然难以捉摸。在这里，我们测量了它对自由基的清除作用，并评价了它对神经细胞免受氧化应激的保护作用。结果表明，ESeroS-GS能有效清除2，2’-azinobis(3-ethylbenzothiazoline)-6-sulfonate自由基(ABTS·+)和2，2-二苯基-1-苦基肼(DPPH)自由基，减轻H_2O_2诱导的神经细胞死亡。H_2O_2诱导溶酶体膜迅速通透，引起溶酶体蛋白酶的重新分布，从而导致神经细胞死亡。ESeroS-GS阻断了TBID与溶酶体膜的相互作用，阻止了TBID向溶酶体膜的转运，减少了其在膜环境中的寡聚化，阻止了溶酶体膜的通透性，从而减轻了神经细胞的死亡。这些数据表明，ESeroS-GS通过稳定溶酶体膜来保护神经细胞免受氧化应激的伤害，从而可能作为一种新的神经保护剂来治疗与氧化应激相关的神经性疾病。
γ-l-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-l-cysteinylglycine sodium salt (ESeroS-GS) is a water-soluble derivative of α-tocopherol (vitamin E). We reported previously that ESeroS-GS can act as an anti-inflammatory agent and can induce cell death in breast cancer cells. However, the potential antioxidant capacities of ESeroS-GS remain elusive. Here, we measured its scavenging effects on free radicals and evaluated its protective effects on neuronal cells against oxidative stress. The results indicated that ESeroS-GS effectively scavenged both 2,2’-azinobis(3-ethylbenzothiazoline)-6-sulfonate free radicals (ABTS•+) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, and attenuated H2O2-induced neuronal cell death. H2O2 treatment induced lysosomal membrane permeabilization rapidly, and caused the redistribution of lysosomal proteases, which were responsible for the neuronal cell death. ESeroS-GS abolished the interaction between tBid and the lysosomal membranes, blocked the translocation of tBid to the lysosomal membranes, decreased its oligomerization within the membrane circumstances, prevented the lysosomal membrane permeabilization, and thus attenuated the neuronal cell death. These data suggest that ESeroS-GS protected the neuronal cells from oxidative stress by stabilizing lysosomal membranes, and thus might act as a novel neuroprotector for neuronal diseases associated with oxidative stress.
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DOI：
10.3390/molecules15117792
发表时间：
2010-11-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Kelsey NA;Wilkins HM;Linseman DA
通讯作者：
Linseman DA
影响因子：
16
作者：
Bhola PD;Letai A
通讯作者：
Letai A
DOI：
10.3390/molecules15053517
发表时间：
2010-05-14
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Iriti M;Vitalini S;Fico G;Faoro F
通讯作者：
Faoro F
DOI：
10.1016/j.bbamcr.2011.01.019
发表时间：
2011-05-01
影响因子：
5.1
作者：
Duan, Wenjuan;Zhou, Juefei;Wei, Taotao
通讯作者：
Wei, Taotao
影响因子：
3.5
作者：
Yan, L;Miao, Q;Yang, FY
通讯作者：
Yang, FY