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The role of amino acid transporters in GSH synthesis in the blood-brain barrier and central nervous system |
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| Authors: | Valdovinos-Flores Cesar Gonsebatt María E |
| Institution: | Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México. |
| Abstract: | Glutathione (GSH) plays a critical role in protecting cells from oxidative stress and xenobiotics, as well as maintaining the thiol redox state, most notably in the central nervous system (CNS). GSH concentration and synthesis are highly regulated within the CNS and are limited by availability of the sulfhydryl amino acid (AA) l-cys, which is mainly transported from the blood, through the blood-brain barrier (BBB), and into neurons. Several antiporter transport systems (e.g., x(c)(-), x(-)(AG), and L) with clearly different luminal and abluminal distribution, Na(+), and pH dependency have been described in brain endothelial cells (BEC) of the BBB, as well as in neurons, astrocytes, microglia and oligodendrocytes from different brain structures. The purpose of this review is to summarize information regarding the different AA transport systems for l-cys and its oxidized form l-cys(2) in the CNS, such as expression and activity in blood-brain barrier endothelial cells, astrocytes and neurons and environmental factors that modulate transport kinetics. |
| Keywords: | AA amino acid AARE amino acids response elements ApN aminopeptidase N ARE antioxidant response element BBB blood–brain barrier BEC brain endothelial cell CNS central nervous system CSF cerebrospinal fluid EC endothelial cell ERK extracellular signal-regulated kinase GCL γ-glutamylcysteine synthetase γGluCys γ-glutamyl-cysteine γGT γ-glutamyl transpeptidase GS GSH synthetase GSH glutathione GTRAP glutamate transporter associated protein GPx glutathione peroxidase l-cys cysteine l-cys2 cystine l-glu glutamate l-gly glycine MAGUK membrane-associated guanylate kinase mTOR mammalian target of rapamycin Nrf2 nuclear factor erythroid-2-related factor PDGF platelet-derived growth factor PI3K phosphoinositide 3-kinase PKA protein kinase A PKB protein kinase B PKC protein kinase C SOD superoxide dismutase TCDD 2 3 7 8-tetrachlorodibenzo-p-dioxin TJ tight junction |
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