Hydrogen peroxide enhances the uptake of polyethylenimine/oligonucleotide complexes in A549 cells by activating CaMKII independent of [Ca(2+)]c elevation.

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.

Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms.

A growing body of scientific evidence indicates that exercise has a positive impact on human health, including neurological health. Aerobic exercise, which is supposed to enhance cardiovascular functions and metabolism, also induces neurotrophic factors that affect hippocampal neurons, thereby improving spatial learning and memory. Alternatively, little is known about the effect of resistance exercise on hippocampus-dependent memory, although this type of exercise is increasingly recommended to improve muscle strength and bone density and to prevent age-related disabilities. Therefore, we evaluated the effects of resistance training on spatial memory and the signaling pathways of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), comparing these effects with those of aerobic exercise. Adult male Wistar rats underwent 8 weeks of aerobic training on a treadmill (AERO group) or resistance training on a vertical ladder (RES group). Control and sham groups were also included. After the training period, both AERO and RES groups showed improved learning and spatial memory in a similar manner. However, both groups presented distinct signaling pathways. Although the AERO group showed increased level of IGF-1, BDNF, TrkB, and ß-CaMKII (calcium/calmodulin-dependent kinase II) in the hippocampus, the RES group showed an induction of peripheral and hippocampal IGF-1 with concomitant activation of receptor for IGF-1 (IGF-1R) and AKT in the hippocampus. These distinct pathways culminated in an increase of synapsin 1 and synaptophysin expression in both groups. These findings demonstrated that both aerobic and resistance exercise can employ divergent molecular mechanisms but achieve similar results on learning and spatial memory.