Effect of Lipopolysaccharide and TNFα on Neuronal Ascorbic Acid Uptake. (5th July 2021)

• Record Type: Journal Article
• Authors: Subramanian, Veedamali S.; Teafatiller, Trevor; Agrawal, Anshu; Kitazawa, Masashi; Marchant, Jonathan S.
• Other Names: Otero-Losada Matilde Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2021(2021)
• Publication Date: 2021-07-05
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2021/4157132
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Vitamin C (ascorbic acid: AA) uptake in neurons occurs via the sodium-dependent vitamin C transporter-2 (SVCT2), which is highly expressed in the central nervous system (CNS). During chronic neuroinflammation or infection, CNS levels of lipopolysaccharide (LPS) and LPS-induced tumor necrosis factor- α (TNF α ) are increased. Elevated levels of LPS and TNF α have been associated with neurodegenerative diseases together with reduced levels of AA. However, little is known about the impacts of LPS and TNF α on neuronal AA uptake. The objective of this study was to examine the effect of LPS and TNF α on SVCT2 expression and function using in vitro and in vivo approaches. Treatment of SH-SY5Y cells with either LPS or TNF α inhibited AA uptake. This reduced uptake was associated with a significant decrease in SVCT2 protein and mRNA levels. In vivo exposure to LPS or TNF α also decreased SVCT2 protein and mRNA levels in mouse brains. Both LPS and TNF α decreased SLC23A2 promoter activity. Further, the inhibitory effect of LPS on a minimal SLC23A2 promoter was attenuated when either the binding site for the transcription factor Sp1 was mutated or cells were treated with the NF- κ B inhibitor, celastrol. We conclude that inflammatory signals suppress AA uptake by impairing SLC23A2 transcription through opposing regulation of Sp1 and NF- κ B factors.