Nitric oxide modulates sodium vitamin C transporter 2 (SVCT-2) protein expression via protein kinase G (PKG) and nuclear factor-κB (NF-κB).

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  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Cyclic GMP-Dependent Protein Kinases/*metabolism ; Gene Expression Regulation/*physiology ; NF-kappa B/*metabolism ; Nerve Tissue Proteins/*metabolism ; Nitric Oxide/*metabolism ; Retina/*metabolism ; Sodium-Coupled Vitamin C Transporters/*metabolism; Animals ; Ascorbic Acid/genetics ; Ascorbic Acid/metabolism ; Biological Transport, Active/physiology ; Cell Proliferation ; Chick Embryo ; Chickens ; Cyclic GMP-Dependent Protein Kinases/genetics ; NF-kappa B/genetics ; Nerve Tissue Proteins/genetics ; Nitric Oxide/genetics ; Retina/cytology ; Retina/embryology ; Signal Transduction/physiology ; Sodium-Coupled Vitamin C Transporters/genetics
    • Abstract:
      Ascorbate is an important antioxidant, which also displays important functions in neuronal tissues, including the retina. The retina is responsible for the initial steps of visual processing, which is further refined in cerebral high-order centers. The retina is also a prototypical model for studying physiologic aspects of cells that comprise the nervous system. Of major importance also is the cellular messenger nitric oxide (NO). Previous studies have demonstrated the significance of NO for both survival and proliferation of cultured embryonic retinal cells. Cultured retinal cells express a high-affinity ascorbate transporter, and the release of ascorbate is delicately regulated by ionotropic glutamate receptors. Therefore, we proposed whether there is interplay between the ascorbate transport system and NO signaling pathway in retinal cells. Here we show compelling evidence that ascorbate uptake is tightly controlled by NO and its downstream signaling pathway in culture. NO also modulates the expression of SVCT-2, an effect mediated by cGMP and PKG. Kinetic studies suggest that NO increases the transport capacity for ascorbate, but not the affinity of SVCT-2 for its substrate. Interestingly, NO utilizes the NF-κB pathway, in a PKG-dependent manner, to modulate both SVCT-2 expression and ascorbate uptake. These results demonstrate that NO exerts a fine-tuned control of the availability of ascorbate to cultured retinal cells and strongly reinforces ascorbate as an important bioactive molecule in neuronal tissues.
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    • Accession Number:
      0 (NF-kappa B)
      0 (Nerve Tissue Proteins)
      0 (Sodium-Coupled Vitamin C Transporters)
      31C4KY9ESH (Nitric Oxide)
      EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
      PQ6CK8PD0R (Ascorbic Acid)
    • Publication Date:
      Date Created: 20111102 Date Completed: 20120325 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      PMC3281729
    • Accession Number:
      10.1074/jbc.M111.260166
    • Accession Number:
      22041898