miR-29a differentially regulates cell survival in astrocytes from cornu ammonis 1 and dentate gyrus by targeting VDAC1.
miR-29a differentially regulates cell survival in astrocytes from cornu ammonis 1 and dentate gyrus by targeting VDAC1.
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DOI：
10.1016/j.mito.2016.08.013
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发表时间：
2016-09
期刊：
影响因子：
4.4
通讯作者：
Giffard RG
中科院分区：
文献类型：
--
作者：
Stary CM;Sun X;Ouyang Y;Li L;Giffard RG
海马角氨1区（CA1）神经元易受脑缺血的影响，而齿状回（DG）神经元对脑缺血的抵抗力更强。这种作用是由局部星形胶质细胞介导的，可能反映了分区域海马区miR-29a表达的差异。我们研究了miR-29a对CA1和DG选择性培养的海马星形胶质细胞在葡萄糖剥夺（GD）下存活的作用。CA1星形胶质细胞比DG星形胶质细胞表现出更多的细胞死亡和更大的miR-29a下降。线粒体电压依赖性阳离子通道-1 （VDAC1）是线粒体的调节剂，也是miR-29a的靶点，在线粒体电压依赖性阳离子通道-1 （VDAC1）中观察到互惠变化。在CA1星形胶质细胞中，miR-29a的升高降低了VDAC1，提高了细胞存活率，而VDAC1的下调提高了细胞存活率。最后，通过抑制miR-29a/VDAC1结合来消除miR-29a的保护作用。这些发现表明，CA1对损伤的选择性易感性可能部分归因于CA1星形胶质细胞中有限的miR-29a反应，从而允许vdac1介导的CA1星形胶质细胞功能障碍更大的增加。
Neurons in the cornu ammonis 1 (CA1) region of the hippocampus are vulnerable to cerebral ischemia, while dentate gyrus (DG) neurons are more resistant. This effect is mediated by local astrocytes, and may reflect differences in subregional hippocampal expression of miR-29a. We investigated the role of miR-29a on survival of hippocampal astrocytes cultured selectively from CA1 and DG in response to glucose deprivation (GD). CA1 astrocytes exhibited more cell death and a greater decrease in miR-29a than DG astrocytes. A reciprocal change was observed in the mitochondrial voltage dependent cation channel-1 (VDAC1), a regulator of mitochondria and target of miR-29a. In CA1 astrocytes, increasing miR-29a decreased VDAC1 and improved cell survival, while knockdown of VDAC1 improved survival. Finally, the protective effect of miR-29a was eliminated by inhibition of miR-29a/VDAC1 binding. These findings suggest that the selective vulnerability of the CA1 to injury may be due in part to a limited miR-29a response in CA1 astrocytes, allowing a greater increase in VDAC1-mediated cellular dysfunction in CA1 astrocytes.
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