p62 modulates the intrinsic signaling of UVB-induced apoptosis.
J Dermatol Sci
; 83(3): 226-33, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27368125
ABSTRACT
BACKGROUND:
UVB radiation is the main source of sunburn and skin cancers. Apoptosis eliminates photodamaged cells, and is thus important for preventing epidermal carcinogenesis. The cytoplasmic regulatory protein p62/A170/sequestosome 1 (p62) molecule is involved in a variety of cellular and signaling pathways. p62 is known to be and important in autophagy, but its role in UVB-induced apoptosis remains to be clarified.OBJECTIVE:
To investigate the role of p62 against UVB-induced apoptotic changes, using mouse embryonic fibroblasts (MEFs) derived from p62 homozygous knockout (p62(-/-)) mice.METHODS:
p62(-/-) and wild-type (p62(+/+)) mice and MEFs were subjected to UVB irradiation, and the resultant apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blots.RESULTS:
Apoptosis was decreased in the p62(-/-) MEFs compared to p62(+/+) MEFs in response to UVB treatment. Compared with p62(+/+) MEFs, p62(-/-) MEFs expressed significantly more Bcl-2 and less Bax, and showed increased Src and Stat3 phosphorylation. Our results show that p62 regulates apoptotic pathways by modifying critical signaling intermediates such as Src and Stat3.CONCLUSION:
p62 deficiency [corrected] reduces UVB-induced apoptosis by modulating intrinsic apoptotic signaling through Src phosphorylation.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Pele
/
Raios Ultravioleta
/
Transdução de Sinais
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Apoptose
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Fibroblastos
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Proteína Sequestossoma-1
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article