title: Increased expression of SVCT2 in a new mouse model raises ascorbic acid in tissues and protects against paraquat-induced oxidative damage in lung.
abstract: 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.
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. Fiona.Harrison@Vanderbilt.edu
authors.forename: Fiona Edith
authors.initials: FE
authors.lastname: Harrison
authors.forename: Jennifer Lee
authors.initials: JL
authors.lastname: Best
authors.forename: Martha Elizabeth
authors.initials: ME
authors.lastname: Meredith
authors.forename: Clare Ruth
authors.initials: CR
authors.lastname: Gamlin
authors.forename: Dorin-Bogdan
authors.initials: DB
authors.lastname: Borza
authors.forename: James Marion
authors.initials: JM
authors.lastname: May
authors.forename: James Michael
authors.initials: JM
authors.lastname: May
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics; D001205:Ascorbic Acid / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D028441:F2-Isoprostanes / Q000378:metabolism; D018703:Founder Effect; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009928:Organ Specificity; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000418:Albumins; D028441:F2-Isoprostanes; D012333:RNA, Messenger; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D010269:Paraquat; D001205:Ascorbic Acid