Inhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats.
Inhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats.
复制标题
慢病毒抑制 SENP3 可诱导大鼠实验性蛛网膜下腔出血细胞凋亡的抑制。
DOI：
10.1016/j.brainres.2015.06.032
复制
发表时间：
2015
期刊：
影响因子：
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通讯作者：
Hang Chun-Hua
中科院分区：
文献类型：
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作者：
Yang Yi-Qing;Li Hua;Zhang Xiang-Sheng;Li Wei;Huang Li-Tian;Yu Zhuang;Jiang Tian-Wei;Chen Qiang;Hang Chun-Hua
研究背景蛛网膜下腔出血（Subarachnoid hemorrhage，SAH）是一种高发病率和高死亡率的危及生命的疾病。SUMO特异性蛋白酶3（SENP 3）是泛素样修饰物特异性蛋白酶家族的一员，是一种能使修饰的蛋白质底物发生SUMO化（SUMO共价修饰）的异肽酶。据报道，SUMO-2/3缀合是SUMO化的成员，具有神经保护作用。材料与方法108只SD大鼠随机分为2部分实验组和9个亚组（第1部分：Sham组、SAH组、SAH+NAC组、SAH+溶媒组;第2部分：Sham组、SAH组、SAH+ lv-SENP 3组、SAH +lv-null组、SAH+NS组）。在SAH前7天，向大鼠左侧脑室注射慢病毒以下调SENP 3。将0.3ml未肝素化的自体血注入视交叉前池模拟实验性SAH。检测MDA水平、SOD活性和GSH含量来评价氧化应激水平。Western blot检测SAH后SENP 3和caspase 3的表达，TUNEL染色观察SAH后细胞凋亡。慢病毒抑制SENP 3可抑制实验性蛛网膜下腔出血大鼠的细胞凋亡。结论当SENP 3在高氧化应激状态下积累时，caspase 3随之激活。它导致比生理性更严重的细胞凋亡。
BackgroundSubarachnoid hemorrhage (SAH) is one of the life-threatening diseases with high morbidity and mortality rates. SUMO-specific proteases 3 (SENP3), a member of the small ubiquitin-like modifier specific protease family, was identified as an isopeptidase that deconjugates SUMOylation (The covalent modification by SUMO) of modified protein substrates. It is reported that SUMO-2/3 conjugation, a member of SUMOylation, presented neuroprotection. The study aimed to evaluate the expression of SENP3 and to explore its potential role in SAH.Materials and methodsA total of 108 Sprague Dawley (SD) rats were randomly divided into 2 parts experiment and 9 subgroups (part 1:Sham group, SAH group, SAH+NAC group, SAH+vehicle group; part 2: Sham group, SAH group, SAH+lv-SENP3 group, SAH+lv-null group, SAH+NS group). 7 days before SAH, lentivirus was administrated into rats׳ left lateral ventricle to down-regulate SENP3. Experimental SAH was imitated by injection with 0.3 ml nonheparinized autoblood into the prechiasmatic cistern. MDA levels, SOD activities, and GSH contents were detected to evaluate oxidative stress level. SENP3 and cleaved caspase 3 were detected by western blot, apoptosis was observed by TUNEL staining.ResultsHigh oxidative stress level following SAH induced rising of SENP3. And inhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats.ConclusionWhen SENP3 accumulated by high oxidative stress, caspase 3 activated subsequently. And it leads to more severe apoptosis than physiological.