Protein kinase inhibitor attenuates apoptotic cell death induced by amyloid beta protein in culture of the rat cerebral cortex.
Amyloid beta protein (A beta) is deposited characteristically in the brain of patients with Alzheimer's disease. Effects of protein kinase inhibitors (H-89, H-7, KN-62) on A beta-induced neuronal cell death were examined in primary culture of dissociated cerebral cortical cells. beta(25-35), the active fragment of A beta, induced neuronal cell death with apoptotic features including chromatin condensation and DNA fragmentation. The cell death was attenuated by cycloheximide or by H-89, a specific protein kinase A (PKA) inhibitor, but not by H-7 or KN-62. These data suggest that beta(25-35) induces apoptotic cell death through the PKA-mediated pathway.
Ueda
K
K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Yagami
T
T
Kageyama
H
H
Kawasaki
K
K
D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D011494:Protein Kinases