Homocysteine induces tau hyperphosphorylation in rats.
Epidemiological and clinical data suggest that homocysteine (Hcy) may increase the risk of Alzheimer's disease, but the underlying mechanisms are elusive. To investigate the effect of Hcy on phosphorylation of tau, we injected Hcy into the lateral cerebral ventricle of rats. We found that level of the hyperphosphorylated tau at PHF-1 (Ser396/404) and tau-1 (Ser198/199/202) epitopes was elevated prominently at 6, 9, and 12 h after the injection, and it was recovered to normal at 24 h. Simultaneously, the level of protein phosphatase-2A catalytic subunit (PP-2Ac) was reduced markedly as compared with control. These results imply that Hcy may induce hyperphosphorylation of tau with PP-2Ac involved mechanism.
Luo
Yougen
Y
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhou
Xinwen
X
Yang
Xifei
X
Wang
Jianzhi
J
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism; D013997:Time Factors; D016875:tau Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D016875:tau Proteins; D006710:Homocysteine; D012694:Serine; C514014:Ppp2ca protein, rat; D054648:Protein Phosphatase 2