Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors

The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-d-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of l-arginine, can regulate ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders. In this review, we will focus on the pathophysiological aspects of the neurological disorders regulated by these ion channels and receptors, and their interaction with agmatine in CNS injury.

     

Inhibition of Neuronal Nitric Oxide Synthase by Ethyl Pyruvate in Schwann Cells Protects Against Peripheral Nerve Degeneration

Neurochemical Research - Schwann cells are essential glial cells in the peripheral nervous system (PNS), and dysfunction of Schwann cells can induce various peripheral neurodegenerative diseases....     

Development of a new bicistronic retroviral vector with strong IRES activity

Background  

Internal Ribosome Entry Site (IRES)-based bicistronic vectors are important tools in today's cell biology. Among applications, the expression of two proteins under the control of a unique promoter permits the monitoring of expression of a protein whose biological function is being investigated through the observation of an easily detectable tracer, such as Green Fluorescent Protein (GFP). However, analysis of published results making use of bicistronic vectors indicates that the efficiency of the IRES-controlled expression can vary widely from one vector to another, despite their apparent identical IRES sequences. We investigated the molecular basis for these discrepancies.     

Synthesis, characterization and X-ray crystal structure of [Re(L4)(CO)3]Br · 2CH3OH (L4 = N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine): A model compound for novel cationic Tc(I)-tricarbonyl radiotracers useful for heart imaging

This report describes synthesis and evaluation of cationic complexes, [^99mTc(CO)₃(L)]⁺ (L = N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L1), N-[(15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L2) and N-[(18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L3)) as potential radiotracers for heart imaging. Preliminary results from biodistribution studies in female adult BALB-c mice indicated that the cationic ^99mTc(I)-tricarbonyl complex, [^99mTc(CO)₃(L2)]⁺, has a significant localization in the heart at 60 min post-injection. To understand the coordination chemistry of these bisphosphine ligands with the ^99mTc(I)-tricarbonyl core, we prepared [Re(CO)₃(L4)]Br (L4: N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine) as a model compound. [Re(CO)₃(L4)]Br has been characterized by elemental analysis, IR, ESI-MS, NMR (¹H, ¹³C, ¹H-¹H COSY, and ¹H-¹³C HMQC) methods, and X-ray crystallography. In solid state, [Re(CO)₃(L4)]⁺ has a distorted octahedron coordination geometry with PNP occupying one facial plane. The chelator backbone adopts a “chair” conformation with phosphine-P atoms at equatorial positions and the amine-N at the apical site. In solution, [Re(CO)₃(L4)]⁺ is able to maintain its cationic nature with no dissociation of carbonyl ligands or any of the three PNP donors.     

Defoliation of Centaurea solstitialis Stimulates Compensatory Growth and Intensifies Negative Effects on Neighbors

Efforts to arrest the spread of invasive weeds with herbivory may be hindered by weak effects of the herbivores or strong compensatory responses of the invaders. We conducted a greenhouse experiment to study the effects of defoliation and soil fungi on competition between the invasive weed Centaurea solstitialis and C. solstitialis and Avena barbata, a naturalized Eurasian annual grass, and Nassella pulchra, a native California bunchgrass. Surprisingly, considering the explosive invasion of grasslands by C. solstitialis, Avena and Nassella were strong competitors and reduced the invader’s biomass by 80.2% and 80.1% over all defoliation and soil fungicide treatments, respectively. However, our experiments were conducted in artificial environments where competition was probably accentuated. When fungicide was applied to the soil, the biomass of C. solstitialis was reduced in all treatment combinations, but reduction in the biomass of the invader had no corollary impact on the grasses. There was no overall effect of defoliation on the final biomass of C. solstitialis as the invader compensated fully for severe clipping. In fact, the directional trend of the clipping effect was +6.4% over all treatments after eight weeks. A significant neighbor × soil fungicide × clipping effect suggested that the compensatory response was the strongest without soil fungicide and when C. solstitialis was alone (+ 19%). Our key finding was that the compensatory response of C. solstitialis in all treatments was associated with an increase in the weed’s negative effects on Nassella and Avena – there was a significant decrease in the total biomass of both grasses and the reproductive biomass of Avena in pots with clipped C. solstitialis. Our results were obtained in controlled conditions that may have been conducive to compensatory growth, but they suggest the existence of mechanisms that may allow C. solstitialis, like other Centaurea species, to resist herbivory.     

Correction to: Description of desferrioxamine-producing bacterium Chitinophaga agrisoli sp. nov., isolated from soil

Antonie van Leeuwenhoek -     

FTO-rs9939609 Polymorphism is a Predictor of Future Type 2 Diabetes: A Population-Based Prospective Study

Biochemical Genetics - The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective...