P53-deficient mice are protected against adrenalectomy-induced apoptosis

被引:31
作者
Sakhi, S [1 ]
Gilmore, W [1 ]
Tran, ND [1 ]
Schreiber, SS [1 ]
机构
[1] UNIV SO CALIF,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90033
关键词
adrenalectomy; cell cycle; granule cell; neuronal apoptosis; p53;
D O I
10.1097/00001756-199612200-00047
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
THE p53 tumor suppressor gene, an important regulator of the cell cycle, has been implicated in apoptotic cell death in uitro, and more recently in neuronal degeneration in vivo. The present study investigated the importance of p53 expression in the apoptotic death of hippocampal granule cells following adrenalectomy. Mice, either homozygous or heterozygous for the p53 null allele and wild-type controls were sacrificed 16 days assessed in paraffin sections morphology was after adrenalectomy. Hippocampal morphology was assessed in paraffin sections stained with hematoxylin and eosin. Cells exhibiting features characteristic of apoptosis were evident in hippocampi from wild-type mice. A significant decrease in the number of apoptotic cells was observed in both homozygous and heterozygous mice. These findings demonstrate that absence or attenuation of p53 expression protects granule cells from adrenalectomy-induced apoptosis and, combined with the results of other studies, suggest that p53 is required for certain types of neuronal degeneration.
引用
收藏
页码:233 / 235
页数:3
相关论文
共 24 条
[1]  
CHEN XB, 1995, CANCER RES, V55, P4257
[2]   THYMOCYTE APOPTOSIS INDUCED BY P53-DEPENDENT AND INDEPENDENT PATHWAYS [J].
CLARKE, AR ;
PURDIE, CA ;
HARRISON, DJ ;
MORRIS, RG ;
BIRD, CC ;
HOOPER, ML ;
WYLLIE, AH .
NATURE, 1993, 362 (6423) :849-852
[3]   TUMOR SUPPRESSORS, KINASES AND CLAMPS - HOW P53 REGULATES THE CELL-CYCLE IN RESPONSE TO DNA-DAMAGE [J].
COX, LS ;
LANE, DP .
BIOESSAYS, 1995, 17 (06) :501-508
[4]   ATTENUATION OF P53 EXPRESSION PROTECTS AGAINST FOCAL ISCHEMIC DAMAGE IN TRANSGENIC MICE [J].
CRUMRINE, RC ;
THOMAS, AL ;
MORGAN, PF .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1994, 14 (06) :887-891
[5]   MICE DEFICIENT FOR P53 ARE DEVELOPMENTALLY NORMAL BUT SUSCEPTIBLE TO SPONTANEOUS TUMORS [J].
DONEHOWER, LA ;
HARVEY, M ;
SLAGLE, BL ;
MCARTHUR, MJ ;
MONTGOMERY, CA ;
BUTEL, JS ;
BRADLEY, A .
NATURE, 1992, 356 (6366) :215-221
[6]   ANALYSIS OF CELL CYCLE-RELATED GENE-EXPRESSION IN POSTMITOTIC NEURONS - SELECTIVE INDUCTION OF CYCLIN D1 DURING PROGRAMMED CELL-DEATH [J].
FREEMAN, RS ;
ESTUS, S ;
JOHNSON, EM .
NEURON, 1994, 12 (02) :343-355
[7]   IDENTIFICATION OF P53 AS A SEQUENCE-SPECIFIC DNA-BINDING PROTEIN [J].
KERN, SE ;
KINZLER, KW ;
BRUSKIN, A ;
JAROSZ, D ;
FRIEDMAN, P ;
PRIVES, C ;
VOGELSTEIN, B .
SCIENCE, 1991, 252 (5013) :1708-1711
[8]   Cyclin D1 is an essential mediator of apoptotic neuronal cell death [J].
Kranenburg, O ;
vanderEb, A ;
Zantema, A .
EMBO JOURNAL, 1996, 15 (01) :46-54
[9]   CANCER - P53, GUARDIAN OF THE GENOME [J].
LANE, DP .
NATURE, 1992, 358 (6381) :15-16
[10]   P53-IMMUNOREACTIVE PROTEIN AND P53 MESSENGER-RNA EXPRESSION AFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS [J].
LI, Y ;
CHOPP, M ;
ZHANG, ZG ;
ZALOGA, C ;
NIEWENHUIS, L ;
GAUTAM, S .
STROKE, 1994, 25 (04) :849-856