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.
Pei
Dong-Sheng
DS
Department of Neurobiology and Biophysics, School of Life Science, University of Science and Technology of China, Hefei 230027, China.
Sun
Ya-Feng
YF
Guan
Qiu-Hua
QH
Hao
Zhi-Bin
ZB
Xu
Tian-Le
TL
Zhang
Guang-Yi
GY
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