Nitric Oxide-induced Activation of the Type 1 Ryanodine Receptor Is Critical for Epileptic Seizure-induced Neuronal Cell Death.
Nitric Oxide-induced Activation of the Type 1 Ryanodine Receptor Is Critical for Epileptic Seizure-induced Neuronal Cell Death.
复制标题
DOI：
10.1016/j.ebiom.2016.08.020
复制
发表时间：
2016-09
期刊：
影响因子：
11.1
通讯作者：
Iino M
中科院分区：
文献类型：
--
作者：
Mikami Y;Kanemaru K;Okubo Y;Nakaune T;Suzuki J;Shibata K;Sugiyama H;Koyama R;Murayama T;Ito A;Yamazawa T;Ikegaya Y;Sakurai T;Saito N;Kakizawa S;Iino M
癫痫持续状态 (SE) 是一种危及生命的紧急情况，可导致神经退行性变并伴有神经系统衰弱性疾病。然而，惊厥性 SE 导致神经退行性变的机制尚不完全清楚。研究表明，癫痫发作会导致大脑中一氧化氮 (NO) 水平显着升高，并且 NO 会通过 1 型兰尼碱受体 (RyR1) 诱导内质网释放 Ca2+，这是通过细胞内 Ca2+ 释放通道的 S-亚硝基化发生的。在这里，我们证明，通过对 NO 诱导的 RyR1 细胞内 Ca2+ 释放通道激活进行基因沉默，可以将神经元从癫痫依赖性细胞死亡中拯救出来。此外，丹曲林（RyR1 的抑制剂）可以预防 SE 引起的神经变性。这些结果表明，NO 诱导的 Ca2 + 通过 RyR 释放参与 SE 诱导的神经变性，并为使用 RyR1 抑制剂预防 SE 后的脑损伤提供了理论依据。 NO 诱导的 RyR1 激活对于癫痫发作诱导的神经元细胞死亡至关重要。丹曲林可预防癫痫发作引起的神经退行性变。 RyR1 是一种治疗候选药物，可改善癫痫发作后的脑损伤。癫痫持续状态 (SE) 是一种危及生命的疾病，可能导致神经退行性变。三上等人。报道称，NO 诱导的 1 型兰尼碱受体 (RyR1) 激活与 SE 诱导的神经元死亡有关。此外，RyR1 抑制剂丹曲林被发现可以预防 SE 引起的神经变性。
Status epilepticus (SE) is a life-threatening emergency that can cause neurodegeneration with debilitating neurological disorders. However, the mechanism by which convulsive SE results in neurodegeneration is not fully understood. It has been shown that epileptic seizures produce markedly increased levels of nitric oxide (NO) in the brain, and that NO induces Ca2 + release from the endoplasmic reticulum via the type 1 ryanodine receptor (RyR1), which occurs through S-nitrosylation of the intracellular Ca2 + release channel. Here, we show that through genetic silencing of NO-induced activation of the RyR1 intracellular Ca2 + release channel, neurons were rescued from seizure-dependent cell death. Furthermore, dantrolene, an inhibitor of RyR1, was protective against neurodegeneration caused by SE. These results demonstrate that NO-induced Ca2 + release via RyR is involved in SE-induced neurodegeneration, and provide a rationale for the use of RyR1 inhibitors for the prevention of brain damage following SE. NO-induced activation of RyR1 is critical for seizure-induced neuronal cell death. Dantrolene is protective against neurodegeneration caused by epileptic seizures. RyR1 is a therapeutic candidate to ameliorate the brain damage following seizures. Status epilepticus (SE) is a life-threatening condition that can cause neurodegeneration. Mikami et al. report that NO-induced activation of type 1 ryanodine receptors (RyR1) is involved in SE-induced neuron death. Furthermore, dantrolene, an inhibitor of RyR1, has been found to be protective against neurodegeneration caused by SE.
登录
查看更多内容
影响因子：
64.5
作者：
Durham, William J.;Aracena-Parks, Paula;Hamilton, Susan L.
通讯作者：
Hamilton, Susan L.
影响因子：
4.8
作者：
Aracena-Parks, Paula;Goonasekera, Sanjeewa A.;Hamilton, Susan L.
通讯作者：
Hamilton, Susan L.
影响因子：
5.7
作者：
Dirksen, Sharon J. Hirshey;Larach, Marilyn Green;Pezalski, Tyler
通讯作者：
Pezalski, Tyler
影响因子：
4.8
作者：
Aghdasi, B;Reid, MB;Hamilton, SL
通讯作者：
Hamilton, SL
影响因子：
11.4
作者：
Kakizawa, Sho;Kishimoto, Yasushi;Takeshima, Hiroshi
通讯作者：
Takeshima, Hiroshi