DNA fragmentation is a feature of cystic fibrosis epithelial cells: A disease with inappropriate apoptosis?

被引:44
作者
Maiuri, L
Raia, V
DeMarco, G
Coletta, S
deRitis, G
Londei, M
Auricchio, S
机构
[1] UNIV NAPLES FEDERICO II,DEPT PEDIAT,I-80131 NAPLES,ITALY
[2] KENNEDY INST,SUNLEY DIV IMMUNOL,LONDON,ENGLAND
[3] CHILDRENS HOSP PAUSILIPON,NAPLES,ITALY
关键词
cystic fibrosis; cystic fibrosis transmembrane conductance regulator; DNA fragmentation; apoptosis; programmed cell death;
D O I
10.1016/S0014-5793(97)00347-5
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
Cystic fibrosis (CF) is a single-gene disease caused by mutations in the CFTR gene, which result in disrupted chloride secretions with inspissated mucous secretions by exocrine glands. Nick-end labelling was used to assess DNA fragmentation in 14 CF and 24 control duodenal samples, and in two CF and two control lung tissues. In CF small intestine median 46% (range: 30-82) villus enterocytes show DNA fragmentation (vs. 3% (range: 1-7) in controls P < 0.001) and median 37.5% (range: 23-79) crypt enterocytes show Ki67 antigen (P < 0.001). In CF airways 57% (range: 54-70) of epithelial cells show DNA fragmentation. Inappropriate high DNA fragmentation is a feature of various CF epithelia. This could have great impact in understanding the mechanisms leading to disease. (C) 1997 Federation of European Biochemical Societies.
引用
收藏
页码:225 / 231
页数:7
相关论文
共 29 条
[1]   DEMONSTRATION THAT CFTR IS A CHLORIDE CHANNEL BY ALTERATION OF ITS ANION SELECTIVITY [J].
ANDERSON, MP ;
GREGORY, RJ ;
THOMPSON, S ;
SOUZA, DW ;
PAUL, S ;
MULLIGAN, RC ;
SMITH, AE ;
WELSH, MJ .
SCIENCE, 1991, 253 (5016) :202-205
[2]   NA+ TRANSPORT IN CYSTIC-FIBROSIS RESPIRATORY EPITHELIA - ABNORMAL BASAL RATE AND RESPONSE TO ADENYLATE-CYCLASE ACTIVATION [J].
BOUCHER, RC ;
STUTTS, MJ ;
KNOWLES, MR ;
CANTLEY, L ;
GATZY, JT .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (05) :1245-1252
[3]   REGULATED ENDOCYTOSIS IN A CHLORIDE SECRETORY EPITHELIAL-CELL LINE [J].
BRADBURY, NA ;
JILLING, T ;
KIRK, KL ;
BRIDGES, RJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 262 (03) :C752-C759
[4]  
COLES HSR, 1993, DEVELOPMENT, V118, P777
[5]  
DELLAGASPERA B, 1995, EXP CELL RES, V219, P379
[6]   SUBMUCOSAL GLANDS ARE THE PREDOMINANT SITE OF CFTR EXPRESSION IN THE HUMAN BRONCHUS [J].
ENGELHARDT, JF ;
YANKASKAS, JR ;
ERNST, SA ;
YANG, YP ;
MARINO, CR ;
BOUCHER, RC ;
COHN, JA ;
WILSON, JM .
NATURE GENETICS, 1992, 2 (03) :240-248
[7]   Complexity in a monogenic disease [J].
Estivill, X .
NATURE GENETICS, 1996, 12 (04) :348-350
[8]   CFTR AND OUTWARD RECTIFYING CHLORIDE CHANNELS ARE DISTINCT PROTEINS WITH A REGULATORY RELATIONSHIP [J].
GABRIEL, SE ;
CLARKE, LL ;
BOUCHER, RC ;
STUTTS, MJ .
NATURE, 1993, 363 (6426) :263-266
[9]   IDENTIFICATION OF PROGRAMMED CELL-DEATH INSITU VIA SPECIFIC LABELING OF NUCLEAR-DNA FRAGMENTATION [J].
GAVRIELI, Y ;
SHERMAN, Y ;
BENSASSON, SA .
JOURNAL OF CELL BIOLOGY, 1992, 119 (03) :493-501
[10]   Mutant cystic fibrosis transmembrane conductance regulator inhibits acidification and apoptosis in C127 cells: Possible relevance to cystic fibrosis [J].
Gottlieb, RA ;
Dosanjh, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (08) :3587-3591