Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain.
Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain.
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DOI：
10.1038/cddis.2014.53
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发表时间：
2014-03-27
影响因子：
9
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胎儿酒精综合征是由于发育中的大脑暴露于乙醇而引起的神经和发育障碍。给大鼠幼崽注射阿托伐他汀可减少乙醇诱导的皮质和海马神经元凋亡。植物蛋白渗透调节素减轻了乙醇诱导的细胞色素c、裂解的半胱天冬酶-3和PARP-1的增加。渗透调节素和乙醇通过降低蛋白水平的切割半胱天冬酶-3，胞内[Ca 2 +]cyt和线粒体跨膜电位崩溃，在体内和体外降低乙醇神经毒性，并上调抗凋亡Bcl-2蛋白。渗透素是脂联素的同源物，它通过磷酸化控制能量代谢。脂联素对乙醇诱导的海马神经元凋亡有保护作用。通过siRNA转染，通过受体AdipoR 1或AdipoR 2的信号传导被消除，降低了AdipoR 1和Adiponectin保护神经元免受乙醇诱导的神经变性的能力。AMPK（腺苷一磷酸活化蛋白激酶）的活化剂二甲双胍增加，而AMPK途径的抑制剂化合物C降低了抗乙醇诱导的细胞凋亡的抑制素和脂联素的能力。Osmotin通过激活AMPK信号通路和Bcl-2家族蛋白发挥神经保护作用。AMPK通路的调节，通过抑制素，脂联素，二甲双胍有望作为胎儿酒精综合征的预防性治疗。
Fetal alcohol syndrome is a neurological and developmental disorder caused by exposure of developing brain to ethanol. Administration of osmotin to rat pups reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in vivo and in vitro by reducing the protein levels of cleaved caspase-3, intracellular [Ca2+]cyt, and mitochondrial transmembrane potential collapse, and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced the ability of osmotin and adiponectin to protect neurons against ethanol-induced neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by osmotin, adiponectin, and metformin hold promise as a preventive therapy for fetal alcohol syndrome.