Differential Effects of Extracellular Vesicles from Two Different Glioblastomas on Normal Human Brain Cells.

Glioblastomas (GBMs) are dreadful brain tumors with abysmal survival outcomes. GBM extracellular vesicles (EVs) dramatically affect normal brain cells (largely astrocytes) constituting the tumor microenvironment (TME). We asked if EVs from different GBM patient-derived spheroid lines would differentially alter recipient brain cell phenotypes.

A tale of two tumors: differential, but detrimental, effects of glioblastoma extracellular vesicles (EVs) on normal human brain cells.

Glioblastomas (GBMs) are dreadful brain tumors with abysmal survival outcomes. GBM EVs dramatically affect normal brain cells (largely astrocytes) constituting the tumor microenvironment (TME). EVs from different patient-derived GBM spheroids induced differential transcriptomic, secretomic, and proteomic effects on cultured astrocytes/brain tissue slices as GBM EV recipients.

Macrophage Xanthine Oxidoreductase Links LPS Induced Lung Inflammatory Injury to NLRP3 Inflammasome Expression and Mitochondrial Respiration.

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) remain poorly treated inflammatory lung disorders. Both reactive oxygen species (ROS) and macrophages are involved in the pathogenesis of ALI/ARDS. Xanthine oxidoreductase (XOR) is an ROS generator that plays a central role in the inflammation that contributes to ALI.

Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis.

Grey matter pathology is central to the progression of multiple sclerosis (MS). We discovered that MS plasma immunoglobulin G (IgG) antibodies, mainly IgG1, form large aggregates (>100 nm) which are retained in the flow-through after binding to Protein A. Utilizing an annexin V live-cell apoptosis detection assay, we demonstrated six times higher levels of neuronal apoptosis induced by MS plasma IgG aggregates (n = 190, from two cohorts) compared to other neurological disorders (n = 116) and healthy donors (n = 44).

Varicella Zoster Virus Induces Nuclear Translocation of the Neurokinin-1 Receptor, Promoting Lamellipodia Formation and Viral Spread in Spinal Astrocytes.

Background: Varicella zoster virus (VZV) can present as a myelopathy with spinal astrocyte infection. Recent studies support a role for the neurokinin-1 receptor (NK-1R) in virus infections, as well as for cytoskeletal alterations that may promote viral spread. Thus, we examined the role of NK-1R in VZV-infected primary human spinal astrocytes (HA-sps) to shed light on the pathogenesis of VZV myelopathy.

Glycolysis and oxidative phosphorylation are essential for purinergic receptor-mediated angiogenic responses in vasa vasorum endothelial cells.

Angiogenesis is an energy-demanding process; however, the role of cellular energy pathways and their regulation by extracellular stimuli, especially extracellular nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis (2-deoxyglucose) and oxidative phosphorylation (OXPHOS) (oligomycin, rotenone, and FCCP), we demonstrate that glycolysis and OXPHOS are both essential for angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R agonists, ATP, and 2-methylthioadenosine diphosphate trisodium salt (MeSADP), but not P1 receptor agonist, adenosine, increased glycolytic activity in VVEC (measured by extracellular acidification rate and lactate production).

WITHDRAWN: Kinetics and ion specificity of Na(+)/Ca(2+) exchange mediated by the reconstituted beef heart mitochondrial Na(+)/Ca(2+) antiporter.

The publisher regrets that this article is an accidental duplication of an article that has already been published in Biochim. Biophys. Acta, 1659 (2004) 83-91, doi:10.

Kinetics and ion specificity of Na(+)/Ca(2+) exchange mediated by the reconstituted beef heart mitochondrial Na(+)/Ca(2+) antiporter.

The Na(+)/Ca(2+) antiporter was purified from beef heart mitochondria and reconstituted into liposomes containing fluorescent probes selective for Na(+) or Ca(2+). Na(+)/Ca(2+) exchange was strongly inhibited at alkaline pH, a property that is relevant to rapid Ca(2+) oscillations in mitochondria. The effect of pH was mediated entirely via an effect on the K(m) for Ca(2+).

Functional distinctions between the mitochondrial ATP-dependent K+ channel (mitoKATP) and its inward rectifier subunit (mitoKIR).

The ATP-sensitive potassium channel from the inner mitochondrial membrane (mitoK(ATP)) is a highly selective conductor of K(+) ions. When isolated in the presence of nonionic detergent and reconstituted in liposomes, mitoK(ATP) is inhibited with high affinity by ATP (K((1/2)) = 20-30 microM). We have suggested that holo-mitoK(ATP) is a heteromultimer consisting of an inwardly rectifying K(+) channel (mitoKIR) and a sulfonylurea receptor (Grover, G.

Mitochondrial potassium transport: the K(+) cycle.

Potassium transport plays three distinct roles in mitochondria. Volume homeostasis to prevent excess matrix swelling is a housekeeping function that is essential for maintaining the structural integrity of the organelle. This function is mediated by the K(+)/H(+) antiporter and was first proposed by Peter Mitchell.

Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K(+) channel in cardiac function and cardioprotection.

Coronary artery disease and its sequelae-ischemia, myocardial infarction, and heart failure-are leading causes of morbidity and mortality in man. Considerable effort has been devoted toward improving functional recovery and reducing the extent of infarction after ischemic episodes. As a step in this direction, it was found that the heart was significantly protected against ischemia-reperfusion injury if it was first preconditioned by brief ischemia or by administering a potassium channel opener.

Mechanisms by which opening the mitochondrial ATP- sensitive K(+) channel protects the ischemic heart.

Diazoxide opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel protects the heart against ischemia-reperfusion injury by unknown mechanisms. We investigated the mechanisms by which mitoK(ATP) channel opening may act as an end effector of cardioprotection in the perfused rat heart model, in permeabilized fibers, and in rat heart mitochondria. We show that diazoxide pretreatment preserves the normal low outer membrane permeability to nucleotides and cytochrome c and that these beneficial effects are abolished by the mitoK(ATP) channel inhibitor 5-hydroxydecanoate.