Postsynaptic density protein 95 antisense oligodeoxynucleotides inhibits the activation of MLK3 and JNK3 via the GluR6.PSD-95.MLK3 signaling module after transient cerebral ischemia in rat hippocampus.
In this study, we investigated the effect of PSD-95 antisense oligodeoxynucleotides on the phosphorylation of MLK3, JNK3 and interactions of MLK3 and PSD-95 with kainate receptor (GluR6) by immunoprecipitation and immunoblotting. Transient (15 min) brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. The antisense oligodeoxynucleotides of PSD-95 were administrated to the SD rats once per day for 3 days before ischemia. Our data show that the antisense oligodeoxynucleotides could inhibit phosphorylation of MLK3 and JNK3 and decrease the interactions of MLK3 and PSD-95 with GluR6. These results indicate that PSD-95 plays an important role in the formation of the GluR6.PSD-95.MLK3 signaling module and MLK3 and JNK3 activation in postischemic rat hippocampus.
Department of Neurobiology and Biophysics, School of Life Science, University of Science and Technology of China, Hefei 230027, China.
Dong-Sheng
DS
Pei
Ya-Feng
YF
Sun
Qiu-Hua
QH
Guan
Zhi-Bin
ZB
Hao
Tian-Le
TL
Xu
Guang-Yi
GY
Zhang
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000517:prevention & control*; D020930:MAP Kinase Kinase Kinases; D008297:Male; D008565:Membrane Proteins; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; D000097806:GluK2 Kainate Receptor
D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D008565:Membrane Proteins; D048057:Mitogen-Activated Protein Kinase 10; D020929:Mitogen-Activated Protein Kinase Kinases; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D018092:Kainic Acid Receptors; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; D000097806:GluK2 Kainate Receptor; C501449:Dlg4 protein, rat; C033652:postsynaptic density proteins