Hsp27 and Hsp70 administered in combination have a potent protective effect against FALS-associated SOD1-mutant-induced cell death in mammalian neuronal cells

被引:70
作者
Patel, YJK
Smith, MDP
de Belleroche, J
Latchman, DS
机构
[1] UCL, Inst Child Hlth, Med Mol Biol Unit, London WC1N 1EH, England
[2] UCL, Inst Child Hlth, Neural Plast Unit, London WC1N 1EH, England
[3] Charing Cross Hosp, Imperial Coll Sci Technol & Med, Dept Neuromusc Dis, London W6 8RF, England
[4] Univ London, London WC1E 7HX, England
来源
MOLECULAR BRAIN RESEARCH | 2005年 / 134卷 / 02期
关键词
copper/zinc superoxide dismutase (SOD1); SOD1 mutations G93A and G93R; cell survival apoptosis; neuroprotection; HSV viral gone delivery; heat-shock protein (Hsp); amyotrophic lateral sclerosis;
D O I
10.1016/j.molbrainres.2004.10.028
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterised by the death of motor neurons in the cortex, brainstem, and spinal cord; resulting in progressive muscle weakness, atrophy, and death from respiratory paralysis, usually within 3-5 years of symptom onset. Approximately 10% of ALS cases are familial (FALS). Mutations in superoxide dismutase-1 (SOD 1) cause approximately 20% of FALS cases and there is overwhelming evidence that a toxic gain of function is the cause of the disease. We have previously shown that FALS-associated SOD1 disease mutants enhanced neuronal death in response to a wide range of stimuli tested whereas wt-SOD1 protected against all insults. We demonstrate for the first time that over-expression of either heat shock protein Hsp27 or Hsp70 has a protective effect against SOD1 disease associated mutant-induced cell death. However, over-expression of Hsp27 and Hsp70 together has a greater potent anti-apoptotic effect, than when expressed singly, against the damaging effects of mutant SOD1. Our results indicate that FALS-associated SOD I disease mutants possess enhanced death-inducing properties and lead to increased apoptosis which can be prevented by either the use of specific caspase inhibitors or Hsp27 and/or Hsp70 over-expression. This potent protective effect of Hsp27 and Hsp70 against the FALS-associated SOD1 disease mutants may be of potential therapeutic importance. (c) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:256 / 274
页数:19
相关论文
共 80 条
[51]   Human hsp27, Drosophila hsp27 and human alpha B-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNF alpha-induced cell death [J].
Mehlen, P ;
KretzRemy, C ;
Preville, X ;
Arrigo, AP .
EMBO JOURNAL, 1996, 15 (11) :2695-2706
[52]  
Meriin AB, 1999, MOL CELL BIOL, V19, P2547
[53]   The chaperone function of hsp70 is required for protection against stress-induced apoptosis [J].
Mosser, DD ;
Caron, AW ;
Bourget, L ;
Meriin, AB ;
Sherman, MY ;
Morimoto, RI ;
Massie, B .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (19) :7146-7159
[54]  
Nollen EAA, 1999, MOL CELL BIOL, V19, P2069
[55]   CARDIOPROTECTION BY CU,ZN-SUPEROXIDE DISMUTASE IS LOST AT HIGH-DOSES IN THE REOXYGENATED HEART [J].
OMAR, BA ;
GAD, NM ;
JORDAN, MC ;
STRIPLIN, SP ;
RUSSELL, WJ ;
DOWNEY, JM ;
MCCORD, JM .
FREE RADICAL BIOLOGY AND MEDICINE, 1990, 9 (06) :465-471
[56]   THE CARDIOPROTECTIVE EFFECT OF MN-SUPEROXIDE DISMUTASE IS LOST AT HIGH-DOSES IN THE POSTISCHEMIC ISOLATED RABBIT HEART [J].
OMAR, BA ;
MCCORD, JM .
FREE RADICAL BIOLOGY AND MEDICINE, 1990, 9 (06) :473-478
[57]   Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3 [J].
Pandey, P ;
Farber, R ;
Nakazawa, A ;
Kumar, S ;
Bharti, A ;
Nalin, C ;
Weichselbaum, R ;
Kufe, D ;
Kharbanda, S .
ONCOGENE, 2000, 19 (16) :1975-1981
[58]   Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways [J].
Parcellier, A ;
Gurbuxani, S ;
Schmitt, E ;
Solary, E ;
Garrido, C .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 304 (03) :505-512
[59]   Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase [J].
Park, HS ;
Lee, JS ;
Huh, SH ;
Seo, JS ;
Choi, EJ .
EMBO JOURNAL, 2001, 20 (03) :446-456
[60]   Neuroprotective effects of copper/zinc-dependent superoxide dismutase against a wide variety of death-inducing stimuli and proapoptotic effect of familial amyotrophic lateral sclerosis mutations [J].
Patel, Y ;
Moraes, YC ;
Latchman, D ;
Coffin, R ;
de Belleroche, J .
MOLECULAR BRAIN RESEARCH, 2002, 109 (1-2) :189-197