Edaravone protects against MPP+ -induced cytotoxicity in rat primary cultured astrocytes via inhibition of mitochondrial apoptotic pathway |
| |
Authors: | Chen Hui Wang Sen Ding Jian-Hua Hu Gang |
| |
Institution: | Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China. |
| |
Abstract: | Edaravone (Eda) is a potent scavenger of hydroxyl radicals and has been demonstrated to be beneficial for patients with acute ischemic stroke. This study was set out to investigate whether Eda protect against MPP(+)-induced cytotoxicity in rat primary cultured astrocytes. The results showed that pre-treatment with Eda inhibited astrocytic apoptosis and lactate dehydrogenase release induced by MPP(+) (200 microM). Further study revealed that Eda prevented GSH depletion, down-regulated mRNA expressions of NADPH oxidase membrane subunit gp91 and membrane-translocated subunit p47, and prevented the decreases of state 3 respiration respiration and respiratory control ratio induced by MPP(+), and thereby inhibited reactive oxygen species production evoked by MPP(+). Moreover, Eda could ameliorate mitochondrial respiratory function, restrain, and prevent mitochondrial membrane potential loss induced by MPP(+). Consequently, Eda inhibited releases of cytochrome c and apoptosis-inducing factor induced by MPP(+). Taken together, these findings reveal for the first time that Eda protects against MPP(+)-induced astrocytic apoptosis via decreasing intracellular reactive oxygen species level and subsequently inhibiting mitochondrial apoptotic pathway. The antiapoptosis effects of Eda on astrocytes may provide a new perspective on neuroprotective therapy. |
| |
Keywords: | apoptosis astrocyte edaravone NADPH oxidase reactive oxygen species |
本文献已被 PubMed 等数据库收录! |
|