Overexpression of hsp70i facilitates reactivation of intracellular proteins in neurones and protects them from denaturing stress

被引:37
作者
Beaucamp, N [1 ]
Harding, TC [1 ]
Geddes, BJ [1 ]
Williams, J [1 ]
Uney, JB [1 ]
机构
[1] Univ Bristol, Div Med, BRI, Bristol BS2 8HW, Avon, England
来源
FEBS LETTERS | 1998年 / 441卷 / 02期
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
heat shock protein; adenovirus; neuron; stress; protein folding;
D O I
10.1016/S0014-5793(98)01553-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transfection of neurones with an adenoviral vector (Ad) expressing high levels of hsp70i was shown to protect primary hippocampal cultures from heat stress. To investigate one of the molecular mechanisms which may underlie hsp70i's neuroprotective effects we measured luciferase activity in the presence and absence of hsp70i following heat or chemical inactivation. Luciferase activity was recovered to 80% of control levels in the presence of recombinant hsp70i in vitro. Luciferase activity was also maintained in primary hippocampal neurones exposed to a denaturing stress if transfected with Ad-hsp70i. These results support the hypothesis that hsp70i protects neurones from stress hy interacting with cytosolic proteins and thereby protecting them from inactivation. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:215 / 219
页数:5
相关论文
共 32 条
[1]   Supervising the fold: Functional principles of molecular chaperones [J].
Buchner, J .
FASEB JOURNAL, 1996, 10 (01) :10-19
[2]   CNS STRESS-RESPONSE - TOO HOT TO HANDLE [J].
CHARLES, J ;
MARCUCCILLI ;
MILLER, RJ .
TRENDS IN NEUROSCIENCES, 1994, 17 (04) :135-139
[3]   HUMAN HOMOLOGS OF THE BACTERIAL HEAT-SHOCK PROTEIN DNAJ ARE PREFERENTIALLY EXPRESSED IN NEURONS [J].
CHEETHAM, ME ;
BRION, JP ;
ANDERTON, BH .
BIOCHEMICAL JOURNAL, 1992, 284 :469-476
[4]   Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1 [J].
Cummings, CJ ;
Mancini, MA ;
Antalffy, B ;
DeFranco, DB ;
Orr, HT ;
Zoghbi, HY .
NATURE GENETICS, 1998, 19 (02) :148-154
[5]   HSP70 binding sites in the tumor suppressor protein p53 [J].
Fourie, AM ;
Hupp, TR ;
Lane, DP ;
Sang, BC ;
Barbosa, MS ;
Sambrook, JF ;
Gething, MJH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (31) :19471-19479
[6]   Hsp70 prevents activation of stress kinases - A novel pathway of cellular thermotolerance [J].
Gabai, VL ;
Meriin, AB ;
Mosser, DD ;
Caron, AW ;
Rits, S ;
Shifrin, VI ;
Sherman, MY .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (29) :18033-18037
[7]  
GAO BC, 1991, J BIOL CHEM, V266, P19565
[8]   Long-term gene therapy in the CNS: Reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin [J].
Geddes, BJ ;
Harding, TC ;
Lightman, SL ;
Uney, JB .
NATURE MEDICINE, 1997, 3 (12) :1402-1404
[9]   Persistent transgene expression in the hypothalamus following stereotaxic delivery of a recombinant adenovirus: Suppression of the immune response with cyclosporin [J].
Geddes, BJ ;
Harding, TC ;
Hughes, DS ;
Byrnes, AP ;
Lightman, SL ;
Conde, G ;
Uney, JB .
ENDOCRINOLOGY, 1996, 137 (11) :5166-5169
[10]  
GEORGOPOULOS C, 1993, ANNU REV CELL BIOL, V9, P601, DOI 10.1146/annurev.cellbio.9.1.601