Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.

Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.

[Transport of zwitterionic amino acids in mammalian cells]. / Transporte de aminoácidos zwitteriónicos en células de mamíferos.

Amino acid transport is an important metabolic process that regulates the amino acid flux between the extracellular and intracellular space of the cell. Amino acids enter to the cell through plasmatic membrane proteins that have been kinetically well characterized. System A is involved in the transport of zwitterionic amino acids with short lateral chains and plays a key role in the gluconeogenesis from amino acids, especially from alanine, and has been implicated in the process of cellular duplication. System N transports amino acids with a nitrogen side chain, specially glutamine, an important regulator of protein synthesis. System L allows the entrance of zwitterionic amino acids with large side chains: it is normally constitutive and it is important for the uptake of these amino acids into the brain where some of them are precursors of neurotransmitters. Amino acid transport has been studied at a molecular level since several cDNAs have been cloned opening the possibility to study their structure and regulation. Several isoforms of some zwitterionic amino acids have been cloned including systems ASC, Gly, beta and proline, which have been classified as a superfamily of carrier proteins containing 6 to 12 spanning membrane domains. This review shows the general aspects of amino acid transport and recent advances in the zwitterionic amino acid transport systems, emphasizing the molecular characteristics of cloned systems and their regulatory factors.

[New concepts in anionic and cationic amino acid transport]. / Nuevos conocimientos del transporte de aminoácidos aniónicos y catiónicos.

In mammalian cells, amino acids are taken up by different transport systems present in the plasma membrane. The transport systems were originally characterized by kinetic and competition studies. However, it was difficult to assign specific amino acids to specific transport systems. With recent advances in molecular biology, it has been possible to identify the specific transporter proteins for specific amino acids. In this review we describe the anionic and cationic amino acid transport systems reported at the molecular level. The anionic amino acids are movilized mainly by the XaG- and Xc- systems which are important in the inactivation of glutamatergic nervous transmission in the brain and for the synthesis of glutathione, respectively. Four isoforms of the XAG- system in the brain belong to the family of Na+ dependent amino acid transporters. Transport systems for cationic amino acids also recognize zwitterionic substrates, and the better characterized systems at the present time are y+, y+L, bo,+ and Bo,+. The regulation of the entrance of cationic amino acid such as arginine, lysine, and ornithine to the cell is important in the biosynthesis of nitric oxide, creatine, carnitine, and polyamines. An inherited defect associated to bo,+ system is cysteinuria.