Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice
Journal of Veterinary Science
;
: 309-317, 2011.
Artigo
em Inglês
| WPRIM
| ID: wpr-17406
ABSTRACT
Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Administração por Inalação
/
Camundongos Transgênicos
/
Terapia Genética
/
Regulação da Expressão Gênica
/
Genes Reporter
/
Técnicas de Transferência de Genes
/
Aerossóis
/
Proteínas Proto-Oncogênicas c-akt
/
Técnicas de Silenciamento de Genes
/
Injeções Intraperitoneais
Limite:
Animais
Idioma:
Inglês
Revista:
Journal of Veterinary Science
Ano de publicação:
2011
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS