Post-ischemic administration of 5-methoxyindole-2-carboxylic acid at the onset of reperfusion affords neuroprotection against stroke injury by preserving mitochondrial function and attenuating oxidative stress.
Post-ischemic administration of 5-methoxyindole-2-carboxylic acid at the onset of reperfusion affords neuroprotection against stroke injury by preserving mitochondrial function and attenuating oxidative stress.
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DOI：
10.1016/j.bbrc.2018.02.106
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发表时间：
2018-02-26
影响因子：
3.1
通讯作者：
Yan LJ
中科院分区：
文献类型：
--
作者：
Wu J;Jin Z;Yang X;Yan LJ
我们之前报道过5-甲氧基吲哚-2-羧酸（MICA）可以在大鼠缺血脑中诱导预处理作用。在本研究中，我们解决了 MICA 是否也能引发缺血性中风后处理效应的问题。为此，在大鼠脑缺血 1 小时后再灌注 24 小时开始时，腹腔注射 MICA（100 mg/kg 体重）。结果表明，用 MICA 治疗的中风动物比用媒介物治疗的动物显示出更少的脑梗塞体积。进一步的实验表明，在 MICA 治疗组中，脑线粒体复合物 I 和 IV 显示出酶活性升高，并且复合物 I 活性的升高可能是由于许多复合物 I 亚基的表达似乎增强所致，这是通过质谱肽测序确定的。与媒介物处理的大鼠相比，复合物 I 和 IV 活性的保留伴随着线粒体膜电位的增强、ATP 产生的增加和 caspase-3 活性的降低。其他研究还表明，在这种 MICA 后处理范例中，Nrf2 信号通路参与了 NQO1 的上调。因此，检测到 MICA 治疗组的氧化应激减弱，表现为 H2O2 产生、蛋白质羰基化和脂质过氧化的减少。综上所述，本研究表明，MICA 还可以在大鼠缺血脑中诱导后处理效应，其潜在机制可能涉及线粒体功能的保存、细胞抗氧化能力的上调和氧化应激的减弱。
We previously reported that 5-methoxyindole-2-carboxylic acid (MICA) could induce preconditioning effect in the ischemic brain of rat. In the present study, we addressed the question of whether MICA could also trigger a postconditioning effect in ischemic stroke. To this end, MICA (100 mg/kg body weight) was injected intraperitoneally at the onset of 24 h reperfusion following 1 h ischemia in rat brain. Results indicate that stroked animals treated with MICA showed less brain infarction volume than that of vehicle-treated animals. Further experiments revealed that brain mitochondrial complexes I and IV showed elevated enzymatic activities in MICA treated group and the elevation in complex I activity was likely contributed by seemingly enhanced expression of many complex I subunits, which was determined by mass spectral peptide sequencing. When compared with vehicle-treated rats, the preservation of complexes I and IV activities was shown to be accompanied by enhanced mitochondrial membrane potential, increased ATP production, and decreased caspase-3 activity. Additional studies also indicate the involvement of NQO1 upregulation by the Nrf2 signaling pathway in this MICA postconditioning paradigm. Consequently, attenuated oxidative stress in the MICA treated group reflected by decrease in H2O2 production and protein carbonylation and lipid peroxidation was detected. Taken together, the present study demonstrates that MICA can also induce a postconditioning effect in the ischemic brain of rat and the underlying mechanism likely involves preservation of mitochondrial function, upregulation of cellular antioxidative capacity, and attenuation of oxidative stress.
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影响因子：
6.9
作者：
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