Increased expression of SVCT2 in a new mouse model raises ascorbic acid in tissues and protects against paraquat-induced oxidative damage in lung

• Published in: PloS one Vol. 7; no. 4; p. e35623
• Main Authors: Harrison, Fiona Edith, Best, Jennifer Lee, Meredith, Martha Elizabeth, Gamlin, Clare Ruth, Borza, Dorin-Bogdan, May, James Marion, May, James Michael
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-04-2012; Public Library of Science (PLoS)
• Subjects: Acids; Albumin; Albumins - metabolism; Analysis; Animal cognition; Animal tissues; Animals; Anxiety; Anxiety - drug therapy; Anxiety - genetics; Ascorbic acid; Ascorbic Acid - metabolism; Biology; Chemical compounds; Cloning; Cognition - drug effects; Cognition - physiology; Cognitive ability; Diabetes; Endocrinology; Excretion; Extracellular matrix; F2-Isoprostanes - metabolism; Founder Effect; Gene expression; Genetic engineering; Herbicides; Immunoreactivity; Isoprostanes; Kidney - drug effects; Kidney - metabolism; Kidneys; Liver; Liver - drug effects; Liver - metabolism; Localization; Locomotor activity; Lung - drug effects; Lung - metabolism; Lungs; Medicine; Metabolism; Mice; Mice, Transgenic - genetics; Mice, Transgenic - metabolism; Models, Animal; Motor Activity - drug effects; Motor Activity - genetics; Nephrology; Nervous system; Neurosciences; Organ Specificity; Organs; Oxidative stress; Oxidative Stress - drug effects; Paraquat; Paraquat - pharmacology; Physiological aspects; Poisoning; RNA; RNA, Messenger - biosynthesis; Rodents; Sensorimotor system; Sodium; Sodium-Coupled Vitamin C Transporters - genetics; Sodium-Coupled Vitamin C Transporters - metabolism; Stem cells; Transgenic mice; Tubules; Up-Regulation; Vitamin C; United States > US; Tennessee; Nashville Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035623

A new transgenic mouse model for global increases in the Sodium Dependent Vitamin C transporter 2 (SVCT2) has been generated. The SVCT2-Tg mouse shows increased SVCT2 mRNA levels in all organs tested and correspondingly increased ascorbic acid (ASC) levels in all organs except liver. The extent of the increase in transporter mRNA expression differed among mice and among organs. The increased ASC levels did not have any adverse effects on behavior in the SVCT2-Tg mice, which did not differ from wild-type mice on tests of locomotor activity, anxiety, sensorimotor or cognitive ability. High levels of SVCT2 and ASC were found in the kidneys of SVCT2-Tg mice and urinary albumin excretion was lower in these mice than in wild-types. No gross pathological changes were noted in kidneys from SVCT2-Tg mice. SVCT2 immunoreactivity was detected in both SVCT2 and wild-type mice, and a stronger signal was seen in tubules than in glomeruli. Six treatments with Paraquat (3x10 and 3x15 mg/kg i.p.) were used to induce oxidative stress in mice. SVCT2-Tg mice showed a clear attenuation of Paraquat-induced oxidative stress in lung, as measured by F(2)-isoprostanes. Paraquat also decreased SVCT2 mRNA signal in liver, lung and kidney in SVCT2-Tg mice.