Antioxidant N-acetylcysteine DNQX inhibited mixed lineage and AMPA/KA receptor antagonist kinase-3 activation following cerebral ischemia in rat hippocampus

被引:30
作者
Tian, H [1 ]
Zhang, QG [1 ]
Li, HC [1 ]
Zhang, GY [1 ]
机构
[1] Xuzhou Med Coll, Res Ctr Biochem & Mol Biol, Xuzhou 221002, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
cerebral ischemia; mixed lineage kinase-3 (MLK3); activation; rat; ROS; NAC; AMPA/KA receptor; DNQX;
D O I
10.1016/S0168-0102(03)00186-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2003 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
引用
收藏
页码:47 / 53
页数:7
相关论文
共 28 条
  • [1] Brunet A, 1997, ESSAYS BIOCHEM, V32, P1
  • [2] COMPLETE NUCLEOTIDE-SEQUENCE, EXPRESSION, AND CHROMOSOMAL LOCALIZATION OF HUMAN MIXED-LINEAGE KINASE-2
    DOROW, DS
    DEVEREUX, L
    TU, GF
    PRICE, G
    NICHOLL, JK
    SUTHERLAND, GR
    SIMPSON, RJ
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1995, 234 (02): : 492 - 500
  • [3] IDENTIFICATION OF A NEW FAMILY OF HUMAN EPITHELIAL PROTEIN-KINASES CONTAINING 2 LEUCINE ISOLEUCINE-ZIPPER DOMAINS
    DOROW, DS
    DEVEREUX, L
    DIETZSCH, E
    DEKRETSER, T
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 213 (02): : 701 - 710
  • [4] GALLO KA, 1994, J BIOL CHEM, V269, P15092
  • [5] Organization and regulation of mitogen-activated protein kinase signaling pathways
    Garrington, TP
    Johnson, GL
    [J]. CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (02) : 211 - 218
  • [6] Diphosphorylation of extracellular signal-regulated kinases and c-Jun N-terminal protein kinases in brain ischemic tolerance in rat
    Gu, ZL
    Jiang, Q
    Zhang, GY
    Cui, ZC
    Zhu, ZM
    [J]. BRAIN RESEARCH, 2000, 860 (1-2) : 157 - 160
  • [7] Extracellular signal-regulated kinase and c-Jun N-terminal protein kinase in ischemic tolerance
    Gu, ZL
    Jiang, Q
    Zhang, GY
    [J]. NEUROREPORT, 2001, 12 (16) : 3487 - 3491
  • [8] c-Jun N-terminal kinase activation in hippocampal CAI region was involved in ischemic injury
    Gu, ZL
    Jiang, Q
    Zhang, GY
    [J]. NEUROREPORT, 2001, 12 (05) : 897 - 900
  • [9] HOLZMAN LB, 1994, J BIOL CHEM, V269, P30808
  • [10] Signal transduction by the c-Jun N-terminal kinase (JNK) - from inflammation to development
    Ip, YT
    Davis, RJ
    [J]. CURRENT OPINION IN CELL BIOLOGY, 1998, 10 (02) : 205 - 219