Inhibition of beta-amyloid cytotoxicity by midkine.
Midkine (MK) is a neurotrophic and angiogenic growth factor whose expression occurs mainly in fetus. It was reported that MK was present in senile plaques of Alzheimer's disease (AD). To investigate the role of MK during amyloid plaques formation in AD, we examined the in vitro effect of MK on Abeta aggregation and Abeta-induced cytotoxicity. We found that incubation of MK with Abeta resulted in the formation of MK/Abeta complexes. The C-terminus of MK (60-121) played a similar role as the full length MK in complex formation. This interaction of MK and Abeta demonstrated significant inhibition on Abeta self-aggregation. MK also inhibited the cytotoxicity of Abeta on PC12h cells. These findings suggest that MK protects the cells from Abeta-induced cytotoxicity through its complex formation with Abeta. MK is probably expressed to prevent cell death in AD.
Yu
G S
GS
R & D Center, BML, Kawagoe City, Saitama, Japan.
Hu
J
J
Nakagawa
H
H
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D000078792:Midkine; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*; D051381:Rats
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D016207:Cytokines; D009414:Nerve Growth Factors; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D000078792:Midkine