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Titolo:
AUTOCRINE NERVE GROWTH-FACTOR PROTECTS HUMAN KERATINOCYTES FROM APOPTOSIS THROUGH ITS HIGH-AFFINITY RECEPTOR (TRK) - A ROLE FOR BCL-2
Autore:
PINCELLI C; HAAKE AR; BENASSI L; GRASSILLI E; MAGNONI C; OTTANI D; POLAKOWSKA R; FRANCESCHI C; GIANNETTI A;
Indirizzi:
UNIV MODENA,DEPT DERMATOL,VIA POZZO 71 I-41100 MODENA ITALY UNIV MODENA,DEPT BIOMED SCI,SECT GEN PATHOL I-41100 MODENA ITALY UNIV ROCHESTER,DEPT DERMATOL ROCHESTER NY 14627
Titolo Testata:
Journal of investigative dermatology
fascicolo: 6, volume: 109, anno: 1997,
pagine: 757 - 764
SICI:
0022-202X(1997)109:6<757:ANGPHK>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; HUMAN-EPIDERMIS; TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; SUPPRESSES APOPTOSIS; KINASE-ACTIVITY; PSORIATIC SKIN; KIT-LIGAND; EXPRESSION; SURVIVAL;
Keywords:
HACAT CELLS; K252; PROGRAMMED CELL DEATH;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
68
Recensione:
Indirizzi per estratti:
Citazione:
C. Pincelli et al., "AUTOCRINE NERVE GROWTH-FACTOR PROTECTS HUMAN KERATINOCYTES FROM APOPTOSIS THROUGH ITS HIGH-AFFINITY RECEPTOR (TRK) - A ROLE FOR BCL-2", Journal of investigative dermatology, 109(6), 1997, pp. 757-764

Abstract

Normal human keratinocytes synthesize and release nerve growth factor(NGF) and express both the low-and the high-affinity NGF receptor, Because NGF has been shown to rescue certain cell types from programmed cell death, we investigated the role of endogenous NGF in preventing keratinocyte apoptosis, We report here that apoptosis is induced in normal human keratinocytes in culture by blocking endogenous NGF signaling with either anti-NGF neutralizing antibody or K252, a specific inhibitor of the tyrosine kinase high-affinity NGF receptor. Apoptosis was assessed by DNA laddering, electron microscopy, and in situ nick end labeling technique, In anti-NGF-treated keratinocytes, the apoptotic process starts at 96 h, and is maximal at 120 h. After K252 treatment, apoptosis starts at 48 h and peaks at 120 h, Because the product of thebcl-2 proto-oncogene protects many cell types from apoptosis, we measured the levels of this protein in apoptotic keratinocytes, We found that both K252 and anti-NGF antibody strikingly downregulate bcl-2 expression, starting at 72 h. Furthermore, HaCat keratinocytes stably transfected with a plasmid containing bcl-2 cDNA fail to undergo apoptosiswhen treated with K252. These findings show that autocrine NGF acts as a survival factor for human keratinocytes in vitro through its high-affinity NGF receptor, possibly by maintaining constant levels of Bcl-2.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 15:28:22