Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice.
10.4142/jvs.2011.12.4.309
- Author:
Arash MINAI-TEHRANI
1
;
Young Chan PARK
;
Soon Kyung HWANG
;
Jung Taek KWON
;
Seung Hee CHANG
;
Sung Jin PARK
;
Kyeong Nam YU
;
Ji Eun KIM
;
Ji Young SHIN
;
Ji Hye KIM
;
Bitna KANG
;
Seong Ho HONG
;
Myung Haing CHO
Author Information
1. Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. mchotox@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
aerosol delivery;
Akt1;
Clara cell;
ERK;
luciferase activity;
naphthalene
- MeSH:
Administration, Inhalation;
Aerosols;
Animals;
Gene Expression Regulation;
Gene Knockdown Techniques;
Gene Therapy/*methods;
Gene Transfer Techniques;
Genes, Reporter;
Injections, Intraperitoneal;
Luciferases/genetics/*metabolism;
Lung Diseases/*chemically induced;
Male;
Mice;
Mice, Transgenic;
Naphthalenes/administration & dosage/*toxicity;
Proto-Oncogene Proteins c-akt/*administration & dosage/genetics/*metabolism
- From:Journal of Veterinary Science
2011;12(4):309-317
- CountryRepublic of Korea
- Language:English
-
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.
