Parthanatos participates in glutamate-mediated HT22 cell injury and hippocampal neuronal death in kainic acid-induced status epilepticus rats.
Parthanatos participates in glutamate-mediated HT22 cell injury and hippocampal neuronal death in kainic acid-induced status epilepticus rats.
复制标题
DOI：
10.1111/cns.13934
复制
发表时间：
2022-12
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
癫痫发作或癫痫持续状态（SE）可导致海马神经元死亡，这具有有害影响。Parthanatos是一种新形式的程序性细胞死亡，其特征在于聚（ADP-核糖）聚合酶-1（PARP-1）的过度活化、聚ADP-核糖聚合物的过度合成、线粒体去极化和凋亡诱导因子的核转位，在各种神经退行性疾病中观察到，但在癫痫中很少报告。我们的目的是研究parthanatos是否参与癫痫发作诱导的海马神经元死亡的机制。采用谷氨酸介导的兴奋性毒性细胞模型研究癫痫发作诱导细胞损伤的机制。采用海人酸杏仁核注射法建立癫痫大鼠模型。在指定的处理后，对海马组织和HT 22细胞进行相应的生化测试。在体外，谷氨酸时间依赖性诱导HT 22细胞死亡，伴随着parthanatos相关的生化事件。用PJ 34（PARP-1抑制剂）或小干扰RNA介导的PARP-1敲低进行预处理可有效保护HT 22细胞免受谷氨酸诱导的毒性作用，并减弱parthanatos相关的生化事件。抗氧化剂N-乙酰半胱氨酸（NAC）的应用挽救了HT 22细胞死亡并逆转了与parthanatos相关的生化事件。在体内，PJ 34和NAC提供针对SE诱导的海马神经元损伤的保护，并抑制与parthanatos相关的生化事件。Parthanatos参与大鼠癫痫发作后谷氨酸诱导的HT 22细胞损伤和海马神经元损伤ROS可能是死亡的始动因素。本研究表明，parthanatos参与了谷氨酸诱导的HT 22细胞损伤和海马神经元损伤在大鼠癫痫发作后。另外，ROS可能是致死过程中的启动因子。这些发现强调了针对癫痫中PARP活性的药理学干预的强大神经保护潜力，并提供了需要在未来研究中验证的多种潜在治疗靶点。
Epileptic seizures or status epilepticus (SE) can cause hippocampal neuronal death, which has detrimental effects. Parthanatos, a new form of programmed cell death, is characterized by hyperactivation of poly (ADP‐ribose) polymerase‐1 (PARP‐1), excessive synthesis of poly ADP‐ribose polymer, mitochondrial depolarization, and nuclear translocation of apoptosis‐inducing factor, observed in various neurodegenerative disorders but rarely reported in epilepsy. We aimed to investigate whether parthanatos participates in the mechanism of seizure‐induced hippocampal neuronal death. Glutamate‐mediated excitotoxicity cell model was used to study the mechanism of seizure‐induced cell injury. Injection of kainic acid into the amygdala was used to establish the epileptic rat model. Corresponding biochemical tests were carried out on hippocampal tissues and HT22 cells following indicated treatments. In vitro, glutamate time‐dependently induced HT22 cell death, accompanied by parthanatos‐related biochemical events. Pretreatment with PJ34 (PARP‐1 inhibitor) or small interfering RNA‐mediated PARP‐1 knockdown effectively protected HT22 cells against glutamate‐induced toxic effects and attenuated parthanatos‐related biochemical events. Application of the antioxidant N‐acetylcysteine (NAC) rescued HT22 cell death and reversed parthanatos‐related biochemical events. In vivo, PJ34 and NAC afforded protection against SE‐induced hippocampal neuronal damage and inhibited parthanatos‐related biochemical events. Parthanatos participates in glutamate‐induced HT22 cell injury and hippocampal neuronal damage in rats following epileptic seizures. ROS might be the initiating factor during parthanatos. The present study demonstrated that parthanatos participated in glutamate‐induced HT22 cell injury and hippocampal neuronal damage in rats following epileptic seizures. In addition, ROS might be the initiating factor in the process of parthanatos. The findings highlight the robust neuroprotective potential of pharmacological interventions targeting PARP activity in epilepsy and provide multiple potential therapeutic targets that need to be verified in future studies.
登录
查看更多内容
影响因子：
4.6
作者：
Mohammad G;Siddiquei MM;Abu El-Asrar AM
通讯作者：
Abu El-Asrar AM
DOI：
10.2741/3297
发表时间：
2009-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
David KK;Andrabi SA;Dawson TM;Dawson VL
通讯作者：
Dawson VL
DOI：
10.1073/pnas.0606526103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Andrabi, Shaida A.;Kim, No Soo;Dawson, Ted M.
通讯作者：
Dawson, Ted M.
影响因子：
4.6
作者：
Salehi F;Behboudi H;Kavoosi G;Ardestani SK
通讯作者：
Ardestani SK
影响因子：
3.7
作者：
Kumari S;Mehta SL;Li PA
通讯作者：
Li PA