title: Nitric oxide modulates sodium vitamin C transporter 2 (SVCT-2) protein expression via protein kinase G (PKG) and nuclear factor-κB (NF-κB).
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.
authors: Department of Neurobiology and Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói, RJ 24001-970, Brazil.
authors: Camila Cabral
authors: CC
authors: Portugal
authors: Thaísa Godinho
authors: TG
authors: da Encarnação
authors: Renato
authors: R
authors: Socodato
authors: Sarah Rodrigues
authors: SR
authors: Moreira
authors: Dan
authors: D
authors: Brudzewsky
authors: António Francisco
authors: AF
authors: Ambrósio
authors: Roberto
authors: R
authors: Paes-de-Carvalho
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000235:genetics / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology; D049109:Cell Proliferation; D002642:Chick Embryo; D002645:Chickens; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D060347:Sodium-Coupled Vitamin C Transporters; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D001205:Ascorbic Acid