GADD45 is induced in Alzheimer's disease, and protects against apoptosis in vitro

被引:52
作者
Torp, R [1 ]
Su, JH
Deng, GM
Cotman, CW
机构
[1] Univ Oslo, Dept Anat, Inst Basic Med Sci, N-0317 Oslo, Norway
[2] Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA 92717 USA
关键词
D O I
10.1006/nbdi.1998.0201
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Expression of the growth arrest DNA damage-inducible protein, GADD45, has recently been reported to be induced by a wide range of stimuli, especially those that produce a high level of base pair damage. We have investigated the expression of GADD45 in brain tissue obtained from patients suffering from Alzheimer's disease (AD). Our results demonstrate that many neurons express the GADD45 protein, and that expression of this protein in neurons is associated with expression of the anti-apoptotic protein Bcl-2, and the presence of DNA damage, but not closely associated with tangle-bearing neurons. Additionally, cell lines overexpressing this protein confer resistance to apoptosis induced by DNA damage agent, suggesting that this protein may participate in cell survival mechanisms. (C) 1998 Academic Press.
引用
收藏
页码:245 / 252
页数:8
相关论文
共 36 条
[1]   DNA damage and apoptosis in Alzheimer's disease: Colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay [J].
Anderson, AJ ;
Su, JH ;
Cotman, CW .
JOURNAL OF NEUROSCIENCE, 1996, 16 (05) :1710-1719
[2]  
BARR PJ, 1994, BIO-TECHNOL, V12, P487, DOI 10.1038/nbt0594-487
[3]   Stress responses to DNA damaging agents in the human colon carcinoma cell line, RKO [J].
Beard, SE ;
Capaldi, SR ;
Gee, P .
MUTATION RESEARCH-GENETIC TOXICOLOGY, 1996, 371 (1-2) :1-13
[4]   ARE REACTIVE OXYGEN SPECIES INVOLVED IN ALZHEIMERS-DISEASE [J].
BENZI, G ;
MORETTI, A .
NEUROBIOLOGY OF AGING, 1995, 16 (04) :661-674
[5]   DNA-DAMAGE, MUTATION AND FINE-STRUCTURE DNA-REPAIR IN AGING [J].
BOHR, VA ;
ANSON, RM .
MUTATION RESEARCH-DNAGING GENETIC INSTABILITY AND AGING, 1995, 338 (1-6) :25-34
[6]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].
BRAAK, H ;
BRAAK, E .
ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259
[7]   ABNORMAL TAU-PHOSPHORYLATION AT SER(396) IN ALZHEIMERS-DISEASE RECAPITULATES DEVELOPMENT AND CONTRIBUTES TO REDUCED MICROTUBULE-BINDING [J].
BRAMBLETT, GT ;
GOEDERT, M ;
JAKES, R ;
MERRICK, SE ;
TROJANOWSKI, JQ ;
LEE, VMY .
NEURON, 1993, 10 (06) :1089-1099
[8]   IMAGE-ANALYSIS OF BETA-AMYLOID LOAD IN ALZHEIMERS-DISEASE AND RELATION TO DEMENTIA SEVERITY [J].
CUMMINGS, BJ ;
COTMAN, CW .
LANCET, 1995, 346 (8989) :1524-1528
[9]   Aging, metabolism, and Alzheimer disease: Review and hypotheses [J].
Finch, CE ;
Cohen, DM .
EXPERIMENTAL NEUROLOGY, 1997, 143 (01) :82-102
[10]   DNA DAMAGE-INDUCIBLE TRANSCRIPTS IN MAMMALIAN-CELLS [J].
FORNACE, AJ ;
ALAMO, I ;
HOLLANDER, MC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (23) :8800-8804