Ammonia Reduces Intracellular Asymmetric Dimethylarginine in Cultured Astrocytes Stimulating Its y⁺LAT2 Carrier-Mediated Loss

International Journal of Molecular Sciences
Krzysztof MilewskiMagdalena Zielińska

Abstract

Previously we had shown that ammonia stimulates nitric oxide (NO) synthesis in astrocytes by increasing the uptake of the precursor amino acid, arginine via the heteromeric arginine/glutamine transporter y⁺LAT2. Ammonia also increases the concentration in the brain of the endogenous inhibitor of nitric oxide synthases (NOS), asymmetric dimethylarginine (ADMA), but distribution of ADMA surplus between the intraastrocytic and extracellular compartments of the brain has not been studied. Here we tested the hypothesis that ammonia modulates the distribution of ADMA and its analog symmetric dimethylarginine (SDMA) between the two compartments of the brain by competition with arginine for the y⁺LAT2 transporter. In extension of the hypothesis we analyzed the ADMA/Arg interaction in endothelial cells forming the blood-brain barrier. We measured by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) technique the concentration of arginine, ADMA and SDMA in cultured cortical astrocytes and in a rat brain endothelial cell line (RBE-4) treated with ammonia and the effect of silencing the expression of a gene coding y⁺LAT2. We also tested the expression of ADMA metabolism enzymes: protein arginine methyltransferase (PR...Continue Reading

References

May 8, 1998·Neurochemical Research·A S Hazell, M D Norenberg
Feb 1, 1997·Nitric Oxide : Biology and Chemistry·E I ClossU Förstermann
Oct 10, 2001·Journal of Neuroscience Research·C R MurthyM D Norenberg
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Mar 30, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Freimut SchliessDieter Häussinger
Oct 11, 2003·Biochemical and Biophysical Research Communications·L C JonesP Vallance
Nov 24, 2004·Metabolic Brain Disease·Alan H Lockwood
Feb 1, 2006·Vascular Medicine·Veli-Pekka ValkonenReijo Laaksonen
Feb 1, 2006·Vascular Medicine·Tom Teerlink
May 5, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·A R JayakumarM D Norenberg
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rajeshwar P MookerjeeRajiv Jalan
May 8, 2007·Pharmacology & Therapeutics·Stefanie M Bode-BögerLouis J Ignarro
Aug 19, 2007·Metabolic Brain Disease·Marta LlansolaVicente Felipo
May 29, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Boris GörgDieter Häussinger
Aug 18, 2009·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Tom TeerlinkChristopher S Wilcox
Jul 6, 2010·Free Radical Biology & Medicine·You-Lin TainLi-Tung Huang
Sep 10, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Vairappan BalasubramaniyanRajiv Jalan
Mar 1, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Mariska DavidsTom Teerlink
May 23, 2012·Biochemical and Biophysical Research Communications·Ellen I ClossThomas Münzel
Aug 14, 2012·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Jens Martens-Lobenhoffer, Stefanie M Bode-Böger
Nov 13, 2012·Neurochemistry International·Marta Skowrońska, Jan Albrecht
Jun 27, 2015·Current Medicinal Chemistry·Dimitris TousoulisGerasimos Siasos
Jul 22, 2015·Clinics in Liver Disease·Parth J Parekh, Luis A Balart
Aug 1, 2015·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Seldag BekpinarFigen Gurdol
Sep 4, 2015·World Journal of Gastroenterology : WJG·Paloma LluchPascual Medina
Mar 1, 2016·Nitric Oxide : Biology and Chemistry·Xiaoyu LiuYingjie Chen

❮ Previous
Next ❯

Citations

Dec 12, 2020·Journal of Clinical Medicine·Sofna BanjarnahorRenke Maas

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
PCR
Assay
Protein Assay

Software Mentioned

Graph Pad
GeneTools

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood-Brain Barrier Transport in Neurodegeneration

The blood brain barrier is important for regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the blood brain barrier can be essential for regulating drug movement and dysregulation of these processes may play a role in neurodegeneration. This feed follows the latest research on this topic.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.