Methamphetamine and Inflammatory Cytokines Increase Neuronal Na+/K+-ATPase Isoform 3: Relevance for HIV Associated Neurocognitive Disorders

Methamphetamine (METH) abuse in conjunction with human immunodeficiency virus (HIV) exacerbates neuropathogenesis and accelerates neurocognitive impairments in the central nervous system (CNS), collectively termed HIV Associated Neurocognitive Disorders (HAND). Since both HIV and METH have been implicated in altering the synaptic architecture, this study focused on investigating alterations in synaptic proteins. Employing a quantitative proteomics approach on synaptosomes isolated from the caudate nucleus from two groups of rhesus monkeys chronically infected with simian immunodeficiency virus (SIV) differing by one regimen, METH treatment, we identified the neuron specific Na+/K+-ATPase alpha 1 isoform 3 (ATP1A3) to be up regulated after METH treatment, and validated its up regulation by METH in vitro. Further studies on signaling mechanisms revealed that the activation of ATP1A3 involves the extracellular regulated kinase (ERK) pathway. Given its function in maintaining ionic gradients and emerging role as a signaling molecule, changes in ATP1A3 yields insights into the mechanisms associated with HAND and interactions with drugs of abuse

Nanosecond Pulsed Electric Field Induced Cytoskeleton, Nuclear Membrane and Telomere Damage Adversely Impact Cell Survival

We investigated the effects of nanosecond pulsed electric fields (nsPEF) on three human cell lines and demonstrated cell shrinkage, breakdown of the cytoskeleton, nuclear membrane and chromosomal telomere damage. There was a differential response between cell types coinciding with cell survival. Jurkat cells showed cytoskeleton, nuclear membrane and telomere damage that severely impacted cell survival compared to two adherent cell lines. Interestingly, disruption of the actin cytoskeleton in adherent cells prior to nsPEF exposure significantly reduced cell survival. We conclude that nsPEF applications are able to induce damage to the cytoskeleton and nuclear membrane. Telomere sequences, regions that tether and stabilize DNA to the nuclear membrane, are severely compromised as measured by a pan-telomere probe. Internal pore formation following nsPEF applications has been described as a factor in induced cell death. Here we suggest that nsPEF induced physical changes to the cell in addition to pore formation need to be considered as an alternative method of cell death. We suggest nsPEF electrochemical induced depolymerization of actin filaments may account for cytoskeleton and nuclear membrane anomalies leading to sensitization

Medium effects in the production and pi0 gamma decay of omega-mesons in pA collisions in the GeV region

The omega-resonance production and its pi0 gamma decay in p-A reactions close to threshold is considered within the Intranuclear Cascade (INC) Model. The pi0 gamma invariant mass distribution shows two components which correspond to the omega decay 'inside' and 'outside' the nucleus, respectively. The 'inside' component is distorted by medium effects, which introduce a mass shift as well as collisional broadening for the omega-meson and its decaying pion. The relative contribution of the 'inside' component is analyzed in detail for different kinematical conditions and nuclear targets. It is demonstrated that a measurement of the correlation in azimuthal angle between the pi0 and gamma momenta allows to separate events related to the 'inside' omega decay from different sources of background when uncorrelated pi0's and gamma's are produced.Comment: 24 pages, 11 figure