Sulfiredoxin-1 exerts anti-apoptotic and neuroprotective effects against oxidative stress-induced injury in rat cortical astrocytes following exposure to oxygen-glucose deprivation and hydrogen peroxide.
Sulfiredoxin-1 exerts anti-apoptotic and neuroprotective effects against oxidative stress-induced injury in rat cortical astrocytes following exposure to oxygen-glucose deprivation and hydrogen peroxide.
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Sulfiredoxin-1 在暴露于氧糖剥夺和过氧化氢后，对大鼠皮质星形胶质细胞氧化应激诱导的损伤发挥抗凋亡和神经保护作用。
DOI：
10.3892/ijmm.2015.2205
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发表时间：
2015-07
影响因子：
5.4
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Zhou Y;Zhou Y;Yu S;Wu J;Chen Y;Zhao Y
硫氧还蛋白1（sulfiredoxin 1，Srxn 1）是一种内源性抗氧化蛋白，在脑缺血中起重要的神经保护作用。然而，Srxn 1在脑缺血中的确切作用机制尚未完全阐明。因此，本研究通过将编码短发夹状RNA（shRNA）的慢病毒载体转染大鼠原代皮层星形胶质细胞，使其暴露于氧糖剥夺（OGD）4 h或100 μM过氧化氢（H2 O2）6 h，以构建体外脑缺血损伤模型。我们发现，OGD或H2 O2暴露后，Srxn 1的敲低导致细胞活力下降，如MTS测定所示，细胞损伤增加，如乳酸脱氢酶测定所示，细胞凋亡增加，如Hoechst 33342染色和流式细胞术所示。此外，我们发现，在暴露于OGD或H2 O2后，Srxn 1的敲低导致线粒体跨膜电位（Δ Km）降低，如JC-1染色所示，细胞色素c的胞质表达增加，（Cyt.C）、半胱天冬酶-3、半胱天冬酶-9、聚（ADP-核糖）聚合酶（PARP）和Bax蛋白在蛋白水平表达降低，而抗凋亡蛋白Bcl-2表达降低;这些作用与线粒体凋亡途径密切相关。然而，我们发现，有没有明显的变化，细胞内钙（[Ca 2 +]i）水平和caspase-12的表达后，Srxn 1的敲低。两者合计，从本研究的结果表明，Srxn 1保护原代大鼠皮质星形胶质细胞从OGD-或H2 O2-诱导的凋亡，并涉及线粒体凋亡途径的激活，这表明Srxn 1可能是一个潜在的目标，在治疗脑缺血。
Sulfiredoxin 1 (Srxn1), an endogenous antioxidant protein, plays an important neuroprotective role in cerebral ischemia. However, the exact mechanisms of action of Srxn1 in cerebral ischemia have not yet been fully elucidated. Therefore, in the present study, rat primary cortical astrocytes transfected with a lentiviral vector encoding short hairpin RNA (shRNA) were exposed to oxygen-glucose deprivation (OGD) for 4 h or to 100 μM hydrogen peroxide (H2O2) for 6 h, in order to construct an in vitro model of cerebral ischemia-induced damage. We found that following exposure to OGD or H2O2, the knockdown of Srxn1 resulted in a decrease in cell viability, as shown by MTS assay, an increase in cell damage, as shown by lactate dehydrogenase assay and an increase in cellular apoptosis, as shown by Hoechst 33342 staining and flow cytometry. Furthermore, we found that following exposure to OGD or H2O2, the knockdown of Srxn1 resulted in a decrease in mitochondrial transmembrane potential (Δψm) as indicated by JC-1 staining, an increase in the cytoplasmic expression of cytochrome c (Cyt.C), caspase-3, caspase-9, poly(ADP-ribose) polymerase (PARP) and Bax protein at the protein level, but a decrease in the expression of the anti-apoptotic Bcl-2 protein; these effects were tightly associated with the mitochondrial apoptotic pathway. However, we found that there was no obvious change in the intracellular calcium ([Ca2+]i) levels and caspase-12 expression following the knockdown of Srxn1. Taken together, the results from the present study demonstrate that Srxn1 protects primary rat cortical astrocytes from OGD- or H2O2-induced apoptosis and that involves the activation of the mitochondrial apoptotic pathway, which suggests that Srxn1 may be a potential target in the treatment of cerebral ischemia.
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影响因子：
25
作者：
通讯作者：
--
胡桃醌通过线粒体途径诱导人胃癌SGC-7901细胞凋亡
影响因子：
--
作者：
Ji, Yu-Bin;Qu, Zhong-Yuan;Zou, Xiang
通讯作者：
Zou, Xiang
影响因子：
2.9
作者：
Kawamura, M;Nakajima, W;Takada, G
通讯作者：
Takada, G
影响因子：
4.7
作者：
Kinsner, A;Pilotto, V;Bal-Price, A
通讯作者：
Bal-Price, A
影响因子：
13.8
作者：
Moldoveanu, Tudor;Follis, Ariele Viacava;Kriwacki, Richard W.;Green, Douglas R.
通讯作者：
Green, Douglas R.