title: Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice.
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.
authors: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
authors: Arash
authors: A
authors: Minai-Tehrani
authors: Young-Chan
authors: YC
authors: Park
authors: Soon-Kyung
authors: SK
authors: Hwang
authors: Jung-Taek
authors: JT
authors: Kwon
authors: Seung-Hee
authors: SH
authors: Chang
authors: Sung-Jin
authors: SJ
authors: Park
authors: Kyeong-Nam
authors: KN
authors: Yu
authors: Ji-Eun
authors: JE
authors: Kim
authors: Ji-Young
authors: JY
authors: Shin
authors: Ji-Hye
authors: JH
authors: Kim
authors: Bitna
authors: B
authors: Kang
authors: Seong-Ho
authors: SH
authors: Hong
authors: Myung-Haing
authors: MH
authors: Cho
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009281:Naphthalenes / Q000008:administration & dosage / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000336:Aerosols; D009281:Naphthalenes; C031721:naphthalene; D008156:Luciferases; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt