Attenuation of amyloid beta (Abeta)-induced inhibition of phosphatidylinositol 4-kinase activity by Abeta fragments, Abeta20-29 and Abeta31-35.
We previously reported that pathophysiological concentrations of amyloid beta protein (Abeta25-35, 0.1-10 nM) directly inhibited type II phosphatidylinositol 4-kinase (PI4KII) activity in neuronal plasma membranes, which resulted in the enhanced glutamate neurotoxicity. In the present study, we examined the effects of Abeta fragments, Abeta20-29 and Abeta31-35, on the 10 nM Abeta25-35- or Abeta1-42-induced inhibition of PI4KII activity. Both of the peptide fragments recovered the inhibition of rat brain plasma membrane PI4KII activity over the concentration range of 0.1-5 nM. Such protection by the Abeta fragments was observed in the 10 nM Abeta25-35-induced inhibition of recombinant human PI4KII, suggesting that these Abeta fragments blocked the inhibition on PI4KII molecule. The Abeta25-35-induced enhancement of glutamate neurotoxicity was also completely inhibited in the presence of these fragments. Thus, Abeta20-29 and Abeta31-35 ameliorated the Abeta-enhanced glutamate neurotoxicity probably through attenuation of Abeta-induced inhibition of PI4KII activity.
Wu
Bo
B
Department of Pharmacology, Kansai Medical University, Fumizono-cho 10-15, Moriguchi-City, Osaka 570-8506, Japan.
Kitagawa
Kaori
K
Liu
Bing
B
Zhang
Nan-Yang
NY
Xiong
Zheng-Mei
ZM
Inagaki
Chiyoko
C
D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D015778:Minor Histocompatibility Antigens; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D015778:Minor Histocompatibility Antigens; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C509685:amyloid beta-protein (20-29); C074636:amyloid beta-protein (25-35); C113042:amyloid beta-protein (31-35); D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase