title: Hydrogen peroxide enhances the uptake of polyethylenimine/oligonucleotide complexes in A549 cells by activating CaMKII independent of [Ca(2+)]c elevation.
abstract: Aerosol oligonucleotide therapy has vast potential in pulmonary system diseases. Reactive oxygen species (ROS) play an important role in complex physiological processes such as cell signaling, apoptosis, etc. Therefore, to determine the mechanism of ROS involvement in polyethylenimine/oligonucleotide (PEI/ON) endocytosis in cells, we measured the fluorescence intensities of fluorescein isothiocyanate-labeled ON complexes with PEI and the changes in cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cells after hydrogen peroxide (H2O2) stimulation. Results showed that improved uptake of PEI/ON complexes was independent of the rise of [Ca(2+)]c in A549 cells, including the Ca(2+) inflow and the release of Ca(2+) from intracellular stores induced by 500 μM H2O2. However, the enhanced uptake efficiency was almost completely abolished by the calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor and the microtube depolymerized drug. CaMKII-dependent microtube polymerization may be responsible for the enhanced uptake of PEI/ON complexes in A549 cells under oxidative stress conditions. This study is useful for research aimed at improving aerosol oligonucleotide therapy in pulmonary system diseases.
authors.affiliation: Department of Respiratory Medicine, The General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China zhuangmacn@126.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Respiratory Medicine, The General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China.
authors.forename: W W
authors.initials: WW
authors.lastname: Sun
authors.affiliation: Department of Experimental Medicine, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000280:Administration, Inhalation; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008171:Lung Diseases / Q000188:drug therapy* / Q000473:pathology; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009841:Oligonucleotides; D017382:Reactive Oxygen Species; D011094:Polyethyleneimine; D006861:Hydrogen Peroxide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium