FEBS Letters | |
Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer disease brain and in okadaic acid‐treated SY5Y cells | |
Wang, Yipeng1  Li, Xian Tau1  Grundke-Iqbal, Inge2  Tung, Yunn Chyn2  Wang, Jian-zhi1  Iqbal, Khalid2  | |
[1] Pathophysiology Department, Tongji Medical College, HUST, 13 Hong Kong Road, Hubei, Wuhan 430030, PR China;Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA | |
关键词: Alzheimer disease; Neurofilament; Phosphorylation; Okadaic acid; SH-SY5Y cell; NF; neurofilament; AD; Alzheimer's disease; PP; protein phosphatase; NFP; neurofilament protein; HD; Huntington disease; OA; okadaic acid; PBS; phosphate-buffered saline; BME; β-mercaptoethanol; PMSF; phenylmethylsulfonyl fluoride; IR; immunoreactivity; | |
DOI : 10.1016/S0014-5793(01)02944-1 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
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【 摘 要 】
We investigated the role of neurofilament (NF) proteins in Alzheimer disease (AD) neurofibrillary degeneration. The levels and degree of phosphorylation of NF proteins in AD neocortex were determined by Western blots developed with a panel of phosphorylation-dependent NF antibodies. Levels of all three NF subunits and the degree of phosphorylation of NF-H and NF-M were significantly increased in AD as compared to Huntington disease brains used as control tissue. The increase in the levels of NF-H and NF-M was 1.7- and 1.5-fold (P<0.01) as determined by monoclonal antibody SMI33, and was 1.6-fold (P<0.01) in NF-L using antibody NR4. The phosphorylation of NF-H and NF-M in AD was increased respectively at the SMI31 epitope by 1.6- and 1.9-fold (P<0.05) and at the SMI33 epitope by 2.7- and 1.3-fold (P<0.01 and P<0.05). Essentially similar effects were observed in SY5Y human neuroblastoma cells when treated with okadaic acid, an inhibitor of protein phosphatase (PP)-2A and -1. This is the first biochemical evidence which unambiguously demonstrates the hyperphosphorylation and the accumulation of NF subunits in AD brain, and shows that the inhibition of PP-2A/PP-1 activities can lead to the hyperphosphorylation of NF-H and NF-M subunits.
【 授权许可】
Unknown
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