Senescent keratinocytes die by autophagic programmed cell death.
Am J Pathol
; 174(2): 423-35, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19147823
ABSTRACT
Normal cells reach senescence after a specific time and number of divisions, leading ultimately to cell death. Although escape from this fate may be a requisite step in neoplastic transformation, the mechanisms governing senescent cell death have not been well investigated. We show here, using normal human epidermal keratinocytes, that no apoptotic markers appear with senescence. In contrast, the expression of several proteins involved in the regulation of macroautophagy, notably Beclin-1 and Bcl-2, was found to change with senescence. The corpses occurring at the senescence growth plateau displayed a large central area delimited by the cytokeratin network that contained a huge quantity of autophagic vacuoles, the damaged nucleus, and most mitochondria. 3-methyladenine, an inhibitor of autophagosome formation, but not the caspase inhibitor zVAD, prevented senescent cell death. We conclude that senescent cells do not die by apoptosis, but as a result of high macroautophagic activity that targets the primary vital cell components.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Autofagia
/
Queratinócitos
Limite:
Female
/
Humans
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
França