烟酰胺腺嘌呤二核苷酸磷酸
氧化应激
标记法
红藻氨酸
细胞凋亡
癫痫
磷酸戊糖途径
末端脱氧核苷酸转移酶
生物
化学
细胞生物学
分子生物学
生物化学
糖酵解
神经科学
氧化酶试验
受体
酶
谷氨酸受体
作者
Chunyou Chen,Mei Qin,Linlin Wang,Xuewen Feng,Tao Xing,Chenfeng Qiu,Jin-Gang Zhu
标识
DOI:10.1016/j.bbrc.2019.05.156
摘要
TP53-induced glycolysis and apoptosis regulator (TIGAR) activates the pentose phosphate pathway (PPP), which feeds reduced nicotinamide adenine dinucleotide phosphate (NADPH) to the antioxidant glutathione pathway. Oxidative stress-induced neuronal apoptosis is the pathological basis of several neurological disorders, including epilepsy. To determine the potential anti-epileptic action TIGAR in a rodent kainic acid (KA)-induced seizure model. Seizures were induced by the intra-cerebroventricular injection of KA, followed by injection of empty or TIGAR-expressing lentiviral vectors. Immunofluorescence was used to detect the localization of TIGAR in the cortices and hippocampi, and the expression levels of relevant proteins were determined by Western blotting. Oxidative stress-related markers were detected using commercially available kits. Neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. TIGAR were mainly expressed in the neurons and rarely located in the astrocytes, and increased in the cortices and hippocampi of KA-treated rats in a time-dependent manner. Lentivirus-mediated TIGAR overexpression significantly decreased the oxidative stress and neuronal apoptosis induced by KA, resulting in prolonged seizure latency and lower Racine scores. Our findings indicate that TIGAR has anti-epileptic, anti-oxidant and anti-apoptotic effects, and is therefore a promising therapeutictarget for epilepsy.
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