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

• Published in: Neuroscience letters Vol. 367; no. 1; pp. 71 - 75
• Main Authors: PEI, Dong-Sheng, SUN, Ya-Feng, GUAN, Qiu-Hua, HAO, Zhi-Bin, XU, Tian-Le, ZHANG, Guang-Yi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 26.08.2004
• Subjects: Animals; Biological and medical sciences; Blotting, Western - methods; Disks Large Homolog 4 Protein; Fundamental and applied biological sciences. Psychology; GluK2 Kainate Receptor; Hippocampus - drug effects; Hippocampus - metabolism; Immunoprecipitation - methods; Intracellular Signaling Peptides and Proteins; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - prevention & control; Male; MAP Kinase Kinase Kinases; Medical sciences; Membrane Proteins; Mitogen-Activated Protein Kinase 10 - metabolism; Mitogen-Activated Protein Kinase Kinase Kinase 11; Mitogen-Activated Protein Kinase Kinases - metabolism; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - metabolism; Neurology; Oligodeoxyribonucleotides, Antisense - pharmacology; Oligodeoxyribonucleotides, Antisense - therapeutic use; Phosphorylation - drug effects; Rats; Rats, Sprague-Dawley; Receptors, Kainic Acid - physiology; Signal Transduction - drug effects; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; Nervous system diseases; Rat; Enzyme; Transferases; Rodentia; Central nervous system; Cardiovascular disease; Glutamate receptor; Encephalon; Mixed lineage kinase-3 (MLK3); Vascular disease; Signal transduction; Vertebrata; Cerebral ischemia; Glutamate receptor 6 (GluR6); Mammalia; Ischemia; Kinase; Animal; Postsynaptic density; Hippocampus; Postsynaptic density protein 95 (PSD-95)
• ISSN: 0304-3940; 1872-7972

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.