Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3β but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of τ: Implications for Alzheimer's disease
作者： S. C. Papasozomenos , A. Shanavas
关键词:
摘要: We have shown previously that glycogen synthase kinase-3 beta (GSK-3 beta), cyclin-dependent kinase 5, and c-Jun NH(2)-terminal become overactivated hyperphosphorylate tau in heat-shocked female rats. This hyperphosphorylation of is estrogen-independent, prevented by androgens, similar to Alzheimer's disease. In this study, ovariectomized (OVX) Sprague-Dawley rats (n = 75) received daily injections 10 microg 17 beta-estradiol benzoate (EB), or 250 testosterone propionate (TP), both EB TP, sesame oil (SO) vehicle for 4-6 weeks. assays forebrain homogenates, overactivation GSK-3 at 0-6 h after heat shock toward human recombinant tau, bovine phosphoglycogen peptide 2 was OVX + TP (EB TP) but not sham-OVX SO, EB. Abs against inactive (pSer(9)) activity-enhanced (pTyr(216)) showed marked increase pSer(9)- decrease pTyr(216)-GSK-3 enhanced the 5. The activity gonadal hormone-independent. serum concentrations were 2.53 ng/ml 201 pg/ml EB, respectively. These findings demonstrate prevents inhibiting shock-induced suggest androgens given aging men or, combination with estrogens, postmenopausal women could prevent delay
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sci-hub.se 参考文章(55)
Papasozomenos Sc, Tau protein immunoreactivity in dementia of the Alzheimer type: II. Electron microscopy and pathogenetic implications. Effects of fixation on the morphology of the Alzheimer's abnormal filaments. Laboratory Investigation. ,vol. 60, pp. 375- 389 ,(1989)
K. Hughes, E. Nikolakaki, S.E. Plyte, N.F. Totty, J.R. Woodgett, Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. The EMBO Journal. ,vol. 12, pp. 803- 808 ,(1993) , 10.1002/J.1460-2075.1993.TB05715.X
Jennifer Hammond, Quynh Le, Cynthia Goodyer, Morrie Gelfand, Mark Trifiro, Andrea LeBlanc, Testosterone‐mediated neuroprotection through the androgen receptor in human primary neurons Journal of Neurochemistry. ,vol. 77, pp. 1319- 1326 ,(2001) , 10.1046/J.1471-4159.2001.00345.X
E. Mandelkow, The tangled tale of tau Nature. ,vol. 402, pp. 588- 589 ,(1999) , 10.1038/45095
S.C. Papasozomenos, T. Papasozomenos, Androgens Prevent the Heat Shock-Induced Hyperphosphorylation but not Dephosphorylation of τ in Female Rats. Implications for Alzheimer's Disease Journal of Alzheimer's Disease. ,vol. 1, pp. 147- 153 ,(1999) , 10.3233/JAD-1999-1302
Ernst ter Haar, Joyce T. Coll, Douglas A. Austen, Hsun-Mei Hsiao, Lora Swenson, Jugnu Jain, Structure of GSK3beta reveals a primed phosphorylation mechanism. Nature Structural & Molecular Biology. ,vol. 8, pp. 593- 596 ,(2001) , 10.1038/89624
Michal Hetman, Jane E. Cavanaugh, David Kimelman, Zhengui Xia, Role of Glycogen Synthase Kinase-3β in Neuronal Apoptosis Induced by Trophic Withdrawal The Journal of Neuroscience. ,vol. 20, pp. 2567- 2574 ,(2000) , 10.1523/JNEUROSCI.20-07-02567.2000
A Himmler, Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family. Molecular and Cellular Biology. ,vol. 9, pp. 1389- 1396 ,(1989) , 10.1128/MCB.9.4.1389
T.Nathan Yoganathan, Penny Costello, Xiaoyi Chen, Mojgan Jabali, Jun Yan, Dan Leung, Zaihui Zhang, Arthur Yee, Shoukat Dedhar, Jasbinder Sanghera, Integrin-linked kinase (ILK): a “hot” therapeutic target Biochemical Pharmacology. ,vol. 60, pp. 1115- 1119 ,(2000) , 10.1016/S0006-2952(00)00444-5
Matthew P Coghlan, Ainsley A Culbert, Darren AE Cross, Stacey L Corcoran, John W Yates, Nigel J Pearce, Oliver L Rausch, Gregory J Murphy, Paul S Carter, Lynne Roxbee Cox, David Mills, Murray J Brown, David Haigh, Robert W Ward, David G Smith, Kenneth J Murray, Alastair D Reith, Julie C Holder, Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chemistry & Biology. ,vol. 7, pp. 793- 803 ,(2000) , 10.1016/S1074-5521(00)00025-9