The uptake of cysteine in cultured primary astrocytes and neurons.

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  • Author(s): Shanker G;Shanker G; Allen JW; Mutkus LA; Aschner M
  • Source:
    Brain research [Brain Res] 2001 Jun 01; Vol. 902 (2), pp. 156-63.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 0045503 Publication Model: Print Cited Medium: Print ISSN: 0006-8993 (Print) Linking ISSN: 00068993 NLM ISO Abbreviation: Brain Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam Elsevier/North-Holland Biomedical Press.
    • Subject Terms:
      Amino Acid Transport System X-AG* ; Symporters*; Astrocytes/*metabolism ; Carrier Proteins/*metabolism ; Cells, Cultured/*metabolism ; Central Nervous System/*metabolism ; Cysteine/*pharmacokinetics ; Glutathione/*biosynthesis ; Neurons/*metabolism; Animals ; Animals, Newborn ; Astrocytes/cytology ; Carrier Proteins/drug effects ; Cells, Cultured/cytology ; Central Nervous System/cytology ; Cysteine/metabolism ; Drug Interactions/physiology ; Enzyme Inhibitors/pharmacology ; Glutamate Plasma Membrane Transport Proteins ; Neurons/cytology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Sodium/metabolism ; Sodium/pharmacology ; Sulfur Radioisotopes/pharmacokinetics
    • Abstract:
      One of the vitally important functions of glutathione (GSH) is to adequately protect cells against toxic chemicals, reactive oxygen metabolites and free radical species. The amino acid, cysteine, is the key rate-limiting substrate for the biosynthesis of GSH, and the maintenance of adequate intracellular GSH levels is dependent upon the extracellular availability and transport of cysteine into cells. In the present study, primary cultures of astrocytes and neurons were employed to characterize cysteine transport systems. Both astrocytes and neurons used Na(+)-dependent systems as the major route for cysteine uptake (80-90% of total), while Na(+)-independent uptake represented a minor component of total transport (10-20% of total). Among the Na(+)-dependent systems, X(AG(-)) was the major contributor (approx. 80-90%) for cysteine uptake in both neurons and astrocytes, with a minor contribution from the ASC transport system (Na(+)-dependent neutral amino acid transport system for alanine, serine, and cysteine). In the Na(+)-independent transport systems (10-20% of total cysteine transport), multifunctional ectoenzyme/amino acid transporter gamma-glutamyltranspeptidase (GGT), and the neutral amino acid L-system contributed approximately equally towards cysteine uptake, in both neurons and astrocytes. The present studies demonstrate that astrocytes and neurons accumulate cysteine by both Na(+)-dependent and Na(+)-independent uptake systems, with major uptake occurring through the X(AG(-)) system and minor uptake via the ASC, GGT and L-systems.
    • Grant Information:
      ES 07331 United States ES NIEHS NIH HHS
    • Accession Number:
      0 (Amino Acid Transport System X-AG)
      0 (Carrier Proteins)
      0 (Enzyme Inhibitors)
      0 (Glutamate Plasma Membrane Transport Proteins)
      0 (Reactive Oxygen Species)
      0 (Sulfur Radioisotopes)
      0 (Symporters)
      9NEZ333N27 (Sodium)
      GAN16C9B8O (Glutathione)
      K848JZ4886 (Cysteine)
    • Publication Date:
      Date Created: 20010601 Date Completed: 20010809 Latest Revision: 20190614
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/s0006-8993(01)02342-3
    • Accession Number:
      11384608