Neuroprotection of AG490 in Oxidative Stress-induced Neuronal Death

Oxidative stress induced increases of the free radicals, which has an important role in neuronal death. Free radicals oxidize intracellular molecules, the destabilization of membrane integrity, and the mitochondrial dysfunction. In present study, we investigated whether AG490, a specific Janus kinases 2 (JAK2) inhibitor had an effect on oxidative stress-induced cytotoxicity in cultured primary cortical neurons. AG490 significantly protected neuronal cell death against various oxidative stimuli, such as hydrogen peroxide (H2O2), L-buthionin-S,R-sulfoxamine (BSO), N-methyl-D-aspartic acid (NMDA), and arachidonic acid (AA). Particularly, AG490 completely blocked H2O2-induced neuronal death. To explore the protective mechanism of AG490, the involvement of JAK2 signal pathway, the regulation of reactive oxygen species (ROS), and the effect on mitochondrial functions were examined. AG490 suppressed oxidant-induced JAK2 phosphorylation. In addition, AG490 regulated the increase of intracellular ROS by oxidative stress and AG490 itself has a modest antioxidant action and increased the total glutathione (GSH) level. Furthermore, AG490 significantly abolished the reduction of mitochondrial membrane potential by oxidative stress. Taken together, AG490 had a potent protective effect in oxidative stress-induced neuronal death. The protection mechanism of AG490 can be explained with involvement of JAK2 pathway, directly scavenging ROS and up-regulation of endogenous antioxidants activity, and restored mitochondrial functions.

Author dc:creator

• 김, 아영

Contributors dc:contributor

• 백, 은주
• 대학원 의학과
• 105967

• AG490
• oxidative stress
• cell death
• 산화적 스트레스
• 신경세포사멸

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000002220
000000002220

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1339