Involvement of oxidative stress in the rapid Akt1 regulating a JNK scaffold during ischemia in rat hippocampus.
It has been well documented that the activation of Akt1 and JNK pathways are involved in the neuronal cell death in cerebral ischemia. In this study, we describe a novel interaction between Akt1 and JNK interacting protein 1 (JIP-1). We first detected the interaction of Akt1 and JIP-1 in hippocampus at various time points of ischemia. In the basal state, JIP-1 bind to Akt1, MLK3 at maximum while JIP-1 binds to JNK3 at minimum. Ischemia stimulus decreased the Akt1-JIP-1 interaction and concomitantly increased association between JIP-1 and JNK3. While MLK3 binding to JIP-1 decreased, similar to Akt1-JIP-1 interaction during ischemia. These results indicated that Akt1 interaction with JIP-1 inhibited JIP-1-mediated potentiation of JNK activity by decreasing JIP-1 binding to specific JNK pathway kinases. Akt1 binding to JIP-1 acts as a regulatory gate preventing JNK activation, which is opened under conditions ischemia injury. Administration of antioxidant N-acetylcysteine (NAC) can obviously affected the level of MLK3, JNK3 and Akt1 binding to JIP-1 and JNK3 activation in the hippocampus at 15min ischemia. The findings suggest that Akt1 regulating JNK scaffold and then regulating JNK activation were closely associated with reactive oxygen species (ROS) during cerebral ischemia.
Pan
Jing
J
Research Center for Biochemistry & Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou 221002, Jiangsu, PR China.
Pei
Dong-Sheng
DS
Yin
Xiao-Hui
XH
Hui
Liang
L
Zhang
Guang-Yi
GY
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D006624:Hippocampus / Q000378:metabolism*; D047468:Immunoprecipitation / Q000379:methods; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
D048868:Adaptor Proteins, Signal Transducing; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D051057:Proto-Oncogene Proteins c-akt; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C110528:Mapk8ip1 protein, rat; C494920:Akt1 protein, rat