title: Antioxidant N-acetylcysteine and AMPA/KA receptor antagonist DNQX inhibited mixed lineage kinase-3 activation following cerebral ischemia in rat hippocampus.
abstract: We measured the MLK3 expression, activity and backphosphorylation following cerebral ischemia. Our data showed that MLK3 protein levels were unalterable during ischemia and reperfusion. However, during ischemia MLK3 activity gradually increased and reached its peak at 30 min of ischemia. While its backphosphorylation reduced from 5 min of ischemia to 30 min of ischemia. In addition, we also detected MLK3 alteration at various time points of reperfusion after 15 min of ischemia, which showed that MLK3 activity increased twice, whereas MLK3 backphosphorylation was similarly consistent with its activity during reperfusion. To further analyze the reason of MLK3 activation, antioxidant N-acetylcysteine (NAC) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA)/kainate (KA) receptor antagonist 6,7-dinitroquinoxaline-2,3(1H, 4H)-dione (DNQX) were given to the rats 20 min prior to ischemia. The results illustrated that NAC preferably inhibited the MLK3 activation during the ischemia and the early reperfusion, whereas DNQX effectively attenuated the MLK3 activation of the late reperfusion. We think that MLK3 activation is certainly associated with reactive oxygen species (ROS) and AMPA/KA receptor in response to ischemic insult.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Quanguang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hongchun
authors.initials: H
authors.lastname: Li
authors.forename: Guangyi
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002545:Brain Ischemia / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
chemical_list: D000111:Acetylcysteine; D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D020930:MAP Kinase Kinase Kinases; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C056723:FG 9041