The Differential DRP1 Phosphorylation and Mitochondrial Dynamics in the Regional Specific Astroglial Death Induced by Status Epilepticus.
The Differential DRP1 Phosphorylation and Mitochondrial Dynamics in the Regional Specific Astroglial Death Induced by Status Epilepticus.
复制标题
由状态癫痫诱导的区域特异性星形死亡中的差异DRP1磷酸化和线粒体动力学。
DOI：
10.3389/fncel.2016.00124
复制
发表时间：
2016
影响因子：
5.3
通讯作者：
Kim JE
中科院分区：
文献类型：
--
作者：
Ko AR;Hyun HW;Min SJ;Kim JE
星形胶质细胞变性的反应和易感性与癫痫持续状态（SE）后星形胶质细胞以血流动力学独立的方式的独特性质有关。由于受损的线粒体分裂在有丝分裂、凋亡和程序性坏死中起着重要作用，我们研究了线粒体动力学的独特模式是否参与SE诱导的星形胶质细胞死亡的特征。在本研究中，SE诱导齿状回分子层星形胶质细胞凋亡，伴随线粒体长度减少。与此相反，在CA 1区的clasmatodendritic（自噬）星形胶质细胞显示由SE诱导的线粒体延长。线粒体分裂抑制剂Mdivi-1可有效抑制星形胶质细胞凋亡，而线粒体分裂增强剂WY 14643则可加重星形胶质细胞凋亡，并可促进星形胶质细胞的树枝状细胞结构改变。星形胶质细胞中这些区域特异性线粒体动力学与动力蛋白相关蛋白1（DRP 1;线粒体分裂蛋白）磷酸化密切相关，而与视神经萎缩1（OPA 1;线粒体融合蛋白）表达无关。据我们所知，目前的数据首次证明了DRP 1介导的线粒体分裂在星形胶质细胞损失中的新作用。因此，目前的研究结果表明，差异星形胶质细胞线粒体动力学可能参与SE诱导的星形胶质细胞死亡的独特特征。
The response and susceptibility to astroglial degenerations are relevant to the distinctive properties of astrocytes in a hemodynamic-independent manner following status epilepticus (SE). Since impaired mitochondrial fission plays an important role in mitosis, apoptosis and programmed necrosis, we investigated whether the unique pattern of mitochondrial dynamics is involved in the characteristics of astroglial death induced by SE. In the present study, SE induced astroglial apoptosis in the molecular layer of the dentate gyrus, accompanied by decreased mitochondrial length. In contrast, clasmatodendritic (autophagic) astrocytes in the CA1 region showed mitochondrial elongation induced by SE. Mdivi-1 (an inhibitor of mitochondrial fission) effectively attenuated astroglial apoptosis, but WY14643 (an enhancer of mitochondrial fission) aggravated it. In addition, Mdivi-1 accelerated clasmatodendritic changes in astrocytes. These regional specific mitochondrial dynamics in astrocytes were closely correlated with dynamin-related protein 1 (DRP1; a mitochondrial fission protein) phosphorylation, not optic atrophy 1 (OPA1; a mitochondrial fusion protein) expression. To the best of our knowledge, the present data demonstrate for the first time the novel role of DRP1-mediated mitochondrial fission in astroglial loss. Thus, the present findings suggest that the differential astroglial mitochondrial dynamics may participate in the distinct characteristics of astroglial death induced by SE.