Tyrosine kinase signal modulation: a matter of H2O2 membrane permeability?
Antioxid Redox Signal
; 19(13): 1447-51, 2013 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-23541115
ABSTRACT
Abstract H2O2 produced by extracellular NADPH oxidases regulates tyrosine kinase signaling inhibiting phosphatases. How does it cross the membrane to reach its cytosolic targets? Silencing aquaporin-8 (AQP8), but not AQP3 or AQP4, inhibited H2O2 entry into HeLa cells. Re-expression of AQP8 with silencing-resistant vectors rescued H2O2 transport, whereas a C173A-AQP8 mutant failed to do so. Lowering AQP8 levels affected H2O2 entry into the endoplasmic reticulum, but not into mitochondria. AQP8 silencing also inhibited the H2O2 spikes and phosphorylation of downstream proteins induced by epidermal growth factor. These observations lead to the hypothesis that H2O2 does not freely diffuse across the plasma membrane and AQP8 and other H2O2 transporters are potential targets for manipulating key signaling pathways in cancer and degenerative diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Transdução de Sinais
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Permeabilidade da Membrana Celular
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Peróxido de Hidrogênio
Limite:
Humans
Idioma:
En
Revista:
Antioxid Redox Signal
Assunto da revista:
METABOLISMO
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Itália