Dynamic-related protein 1 inhibitor eases epileptic seizures and can regulate equilibrative nucleoside transporter 1 expression.
Dynamic-related protein 1 inhibitor eases epileptic seizures and can regulate equilibrative nucleoside transporter 1 expression.
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动态相关蛋白 1 抑制剂可缓解癫痫发作并调节平衡核苷转运蛋白 1 表达
DOI：
10.1186/s12883-020-01921-y
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发表时间：
2020-09-22
期刊：
影响因子：
2.6
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Luo Z;Wang J;Tang S;Zheng Y;Zhou X;Tian F;Xu Z
动态相关蛋白1 （dynamic -related protein 1, Drp1）是参与线粒体分裂调控的关键蛋白，它可以影响线粒体的动态平衡，并对癫痫发作时的神经元损伤具有保护作用。平衡核苷转运蛋白1 （ENT1）在线粒体膜中表达并起作用，平衡跨膜的腺苷浓度。Drp1是否通过调节ENT1的功能参与癫痫发作的发病机制尚不清楚。方法本研究采用匹罗卡品诱导大鼠癫痫持续状态（SE），并采用选择性Drp1抑制剂线粒体分裂抑制剂1 （Mdivi-1）抑制匹罗卡品诱导的SE模型的线粒体分裂。在SE诱导前腹腔注射mdivi -1，观察小鼠首次癫痫发作潜伏期及癫痫发作次数。免疫荧光法检测Drp1的分布，Western blot法检测Drp1和ENT1的表达谱。透射电镜观察海马CA1区神经元线粒体超微结构。结果我们发现Drp1主要在神经元中表达，在SE诱导后6 h和24 h，海马和颞叶新皮层组织中Drp1的表达显著上调。线粒体裂变抑制剂1减轻SE诱导后的癫痫发作，减少线粒体损伤和ENT1表达。结论这些数据表明，匹洛卡品诱导SE后海马和颞叶新皮层Drp1表达上调，抑制Drp1可能通过调节匹洛卡品诱导SE后ENT1成为SE的潜在治疗靶点。
BackgroundDynamic-related protein 1 (Drp1) is a key protein involved in the regulation of mitochondrial fission, and it could affect the dynamic balance of mitochondria and appears to be protective against neuronal injury in epileptic seizures. Equilibrative nucleoside transporter 1 (ENT1) is expressed and functional in the mitochondrial membrane that equilibrates adenosine concentration across membranes. Whether Drp1 participates in the pathogenesis of epileptic seizures via regulating function of ENT1 remains unclear.MethodsIn the present study, we used pilocarpine to induce status epilepticus (SE) in rats, and we used mitochondrial division inhibitor 1 (Mdivi-1), a selective inhibitor to Drp1, to suppress mitochondrial fission in pilocarpine-induced SE model. Mdivi-1administered by intraperitoneal injection before SE induction, and the latency to firstepileptic seizure and the number of epileptic seizures was thereafter observed. The distribution of Drp1 was detected by immunofluorescence, and the expression patterns of Drp1 and ENT1 were detected by Western blot. Furthermore, the mitochondrial ultrastructure of neurons in the hippocampal CA1 region was observed by transmission electron microscopy.ResultsWe found that Drp1 was expressed mainly in neurons and Drp1 expression was significantly upregulated in the hippocampal and temporal neocortex tissues at 6 h and 24 h after induction of SE. Mitochondrial fission inhibitor 1 attenuated epileptic seizures after induction of SE, reduced mitochondrial damage and ENT1 expression.ConclusionsThese data indicate that Drp1 is upregulated in hippocampus and temporal neocortex after pilocarpine-induced SE and the inhibition of Drp1 may lead to potential therapeutic target for SE by regulating ENT1 after pilocarpine-induced SE.
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影响因子：
--
作者：
Reddy PH;Reddy TP;Manczak M;Calkins MJ;Shirendeb U;Mao P
通讯作者：
Mao P
影响因子：
2.4
作者：
Kim H;Lee JY;Park KJ;Kim WH;Roh GS
通讯作者：
Roh GS
影响因子：
4.7
作者：
Sharp, Willard W.
通讯作者：
Sharp, Willard W.
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。
影响因子：
5.3
作者：
Ko AR;Hyun HW;Min SJ;Kim JE
通讯作者：
Kim JE
影响因子：
11.8
作者：
Cassidy-Stone, Ann;Chipuk, Jerry E.;Nunnari, Jodi
通讯作者：
Nunnari, Jodi