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Lucie Aumailley, Marie Julie Dubois, Tracy A Brennan, Chantal Garand, Eric R Paquet, Robert J Pignolo, André Marette, Michel Lebel
Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase (WRN). Mice lacking part of the helicase domain of the WRN ortholog exhibit several phenotypic features of WS. In this study, we generated a Wrn mutant line that, like humans, relies entirely on dietary sources of vitamin C (ascorbate) to survive, by crossing them to mice that lack the gulonolactone oxidase enzyme required for ascorbate synthesis. In the presence of 0.01% ascorbate (w/v) in drinking water, double-mutant mice exhibited a severe reduction in lifespan, small size, sterility, osteopenia, and metabolic profiles different from wild-type (WT) mice...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yan Jiao, Mingming Niu, Cheng Tian, Jian Yan, Aron W Vancil, Xuenan Yan, Ming Zhang
Vitamin D (VD) and vitamin C (VC) have been recognized as essential elements for human health.  Animal models, especially mouse models, have been widely used in the study of VD and VC. This study is to investigate how VD and VC interact at molecular level using whole genome expression profiles from spleens of 111 mouse strains and livers from 40 mouse strains. We first identified the genes that are closely correlated to vitamin D receptor (Vdr) and gulonolactone oxidase (Lgo). We next analyzed the potential molecular pathways of Vdrand Lgo correlated genes and examined how these two sets of pathways are connected in liver and spleen...
November 30, 2017: Cellular and Molecular Biology
Xing Ji, Xinhua Hu, Chaochun Zou, Hongfeng Ruan, Xueying Fan, Chao Tang, Wei Shi, Liu Mei, Haibin Zhu, Musaddique Hussain, Linghui Zeng, Xiaodong Zhang, Ximei Wu
BACKGROUND: The hyperglycemia and hyperoxidation that characterize diabetes lead to reduced vitamin C (VC) in diabetic humans and experimentally diabetic animals. Herein, we access the effects of VC deficiency on the diabetic kidney injury and explore the underlying mechanism. METHODS: l-gulonolactone oxidase conventional knockout (Gulo(-/-)) mice genetically unable to synthesize VC were subjected to streptozotocin-induced diabetic kidney injury and the role of VC deficiency was evaluated by biochemical and histological approaches...
September 2017: Biochimica et Biophysica Acta
Chibuisi G Alimba, Raphael D Ajiboye, Olakunle S Fagbenro
Hospital effluents contain myriad of mutagens and genotoxins capable of increasing DNA damage in aquatic biota. African mudfish, Clarias gariepinus, are exposed to genotoxins when cultured in swamps and derelict water bodies often contaminated by effluents. Moreover, its DNA is susceptible to xenobiotic-induced lesions since it lacks L-gulonolactone oxidase and hence cannot synthesize L-ascorbic acid. This study investigated 96-h acute toxicity and protective effects of dietary ascorbic acid (AA) against micronucleus (MN) and abnormal nuclear (NAs) formation in C...
May 19, 2017: Fish Physiology and Biochemistry
Mafalda Maldonado, Eveling Inostroza, Eduardo Peña, Natacha Moncada, Lorena Mardones, José Luis Medina, Alejandra Muñoz, Marcell Gatica, Marcelo Villagrán, Elizabeth Escobar, Pamela Mendoza, Francisco J Roa, Mauricio González, Paula Guzmán, Francisco A Gutiérrez-Castro, Karen Sweet, Carola Muñoz-Montesino, Juan Carlos Vera, Coralia I Rivas
The liver has an extraordinary regenerative capacity in response to partial hepatectomy (PHx), which develops with neither tissue inflammation response nor alterations in the whole organism. This process is highly coordinated and it has been associated with changes in glutathione (GSH) metabolism. However, there are no reports indicating ascorbic acid (AA) levels after partial hepatectomy. AA and GSH act integrally as an antioxidant system that protects cells and tissues from oxidative damage and imbalance observed in a variety of diseases that affect the liver...
April 15, 2017: Free Radical Biology & Medicine
Lucie Aumailley, Alessandra Warren, Chantal Garand, Marie Julie Dubois, Eric R Paquet, David G Le Couteur, André Marette, Victoria C Cogger, Michel Lebel
Suboptimal intake of dietary vitamin C (ascorbate) increases the risk of several chronic diseases but the exact metabolic pathways affected are still unknown. In this study, we examined the metabolic profile of mice lacking the enzyme gulonolactone oxidase (Gulo) required for the biosynthesis of ascorbate. Gulo-/- mice were supplemented with 0%, 0.01%, and 0.4% ascorbate (w/v) in drinking water and serum was collected for metabolite measurements by targeted mass spectrometry. We also quantified 42 serum cytokines and examined the levels of different stress markers in liver...
March 2016: Aging
S J Padayatty, M Levine
Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization...
September 2016: Oral Diseases
Claudia Rasche, Britta Fournes, Uwe Dirks, Karl Speer
Some steps of the QuEChERS method for the analysis of pesticides with GC-MS/MS in cereals and dried fruits were improved or simplified. For the latter, a mixing vessel with stator-rotor-system proved to be advantageous. The extraction procedure of dried fruits is much easier and safer than the Ultra Turrax and results in excellent validation data at a concentration level of 0.01mg/kg (116 of 118 analytes with recoveries in the range of 70-120%, 117 of 118 analytes with RSD <20%). After qualifying problematic lipophilic pesticides in fat-rich cereals (fat content >7%), predominantly organochlorines showed recoveries of <70% in quantification when the standard QuEChERS method with water was used...
July 17, 2015: Journal of Chromatography. A
Biyun Ching, Shit F Chew, Yuen K Ip
Biosynthesis of ascorbate is known to occur in liver and/or kidney of some vertebrates; however, a recent study discovered the expression of l-gulono-γ-lactone oxidase, an enzyme essential for ascorbate synthesis, in the brain of the African lungfish, Protopterus annectens. This report provides an up-to-date review on ascorbate synthesis in fishes and the possible future directions of study in view of the discovery of the unusual site of ascorbate biosynthesis.
February 2015: IUBMB Life
Glen Wheeler, Takahiro Ishikawa, Varissa Pornsaksit, Nicholas Smirnoff
Ascorbic acid (vitamin C) is an enzyme co-factor in eukaryotes that also plays a critical role in protecting photosynthetic eukaryotes against damaging reactive oxygen species derived from the chloroplast. Many animal lineages, including primates, have become ascorbate auxotrophs due to the loss of the terminal enzyme in their biosynthetic pathway, L-gulonolactone oxidase (GULO). The alternative pathways found in land plants and Euglena use a different terminal enzyme, L-galactonolactone dehydrogenase (GLDH)...
2015: ELife
Md Musfiqur Rahman, Jeong-Heui Choi, A M Abd El-Aty, Morad D N Abid, Jong-Hyouk Park, Tae Woong Na, Yong-Doo Kim, Jae-Han Shim
During gas chromatography (GC), the matrix can deactivate the active site during the transport of the compound from the injector to the detector. This deactivation capacity varies among matrices, as it is dependant on the concentrations of the different constituent compounds of each matrix. During the analysis of terbufos and its metabolites, two of its metabolites were highly thermolabile, and were readily decomposed inside the GC system. As the matrix can mask the active site, we carried out a matrix-matched calibration in an effort to protect the analyte against decomposition...
July 15, 2012: Food Chemistry
Bo-jian Chen, Cui-juan Niu, Lin Yuan
Intense temperature change often leads to increased oxidative stress in many animals with a few exceptions, including the turtle. To date, little is known about the mechanism of protective antioxidative defenses in turtles during acute temperature change, specifically the role that the antioxidant ascorbic acid (AA) plays. In this study, Chinese soft-shelled turtles (Pelodiscus sinensis) were initially acclimated at 28°C (3 wks), exposed to acute cold condition (8°C, 8 h) and finally placed in recovery (28°C, 24 h)...
June 2015: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Yue Huang, Xiaodong Zhu, Lishi Wang, Xiaoyun Liu, Lu Lu, Weikuan Gu, Yan Jiao
The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains...
2014: TheScientificWorldJournal
Biyun Ching, Jasmine L Y Ong, You Rong Chng, Xiu Ling Chen, Wai P Wong, Shit F Chew, Yuen K Ip
This study aimed to test the hypothesis that the brain of Protopterus annectens expressed L-gulono-γ-lactone oxidase (gulo/Gulo), the enzyme catalyzing the last step of ascorbate biosynthesis, and could maintain high concentrations of ascorbate during estivation. We cloned and sequenced gulo from the kidney of P. annectens and performed quantitative PCR to determine its mRNA expression in kidney and brain. Gulo activity was assayed and its protein abundance was determined by Western blot using custom-made anti-Gulo antibody...
August 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Britt Tranberg, Axel Kornerup Hansen, Jens Lykkesfeldt
PURPOSE: Vitamin C (vitC) deficiency has been linked to obesity and increased risk of cardiovascular disease and type 2 diabetes. Whereas humans are unable to synthesize vitC and therefore to compensate for increased turnover, we investigated whether mice--independent of dietary vitC--are able to modulate their vitC homeostasis during high-fat (HF) feeding. METHODS: Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention...
September 2014: European Journal of Nutrition
Houli Jiang, Fiona E Harrison, Kavita Jain, Samantha Benjamin, James M May, Joan P Graves, Darryl C Zeldin, John R Falck, Bruce D Hammock, John C McGiff
The cardiovascular effects of vitamin C (VitC) could be mediated by epoxyeicosatrienoic acids (EETs). We aimed to study the mechanism of VitC-dependent microsomal formation of cis- and trans-EETs and the regulation of EET levels in rat isolated perfused kidneys and in vivo. VitC biphasically stimulated rat kidney microsomal cis- and trans-EET formation in a ratio of 1:2, involving the participation of lipid hydroperoxides (LOOHs), Fe(2+), and cytochrome P450 (CYP). Levels of LOOHs correlated with microsomal EET production...
June 1, 2012: Advances in Bioscience and Biotechnology
S-Y Kook, K-M Lee, Y Kim, M-Y Cha, S Kang, S H Baik, H Lee, R Park, I Mook-Jung
Blood-brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply...
2014: Cell Death & Disease
Marcela Vélez-Alavez, Lía C Méndez-Rodriguez, Juan A De Anda Montañez, C Humberto Mejía, Felipe Galván-Magaña, Tania Zenteno-Savín
In fish, vitamins are part of the first line of the antioxidant defense, they are directly related to stress and disease, and they are involved in the maintenance of various physiological processes and metabolic reactions. In general, fish are unable to synthesize vitamin C due to a deficiency in gulonolactone oxidase (GLO), the enzyme responsible for its de novo synthesis. Vitamin E is involved in the immune response and perhaps one of its main physiological functions is to protect membranes from oxidative damage (lipid peroxidation) associated with free radical production...
April 2014: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Yayoi Kagami, Yoshitaka Kondo, Setsuko Handa, Naoki Maruyama, Akihito Ishigami
Senescence marker protein-30 (SMP30) was first described as a physiologic entity that decreases in the rat liver and kidney with aging. Previously, we established that SMP30 is the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in ascorbic acid (AA) biosynthesis. In the present study, we found SMP30/GNL mRNA expressed in the mouse ovary. To ascertain the reason for ovarian SMP30/GNL expression, we examined mice during gestation. SMP30/GNL mRNA expression was evident at the start of gestation, increased for the next eight days then decreased rapidly...
2013: Biological & Pharmaceutical Bulletin
B W Tucker, J E Halver
Although most vertebrate animals synthesize L-ascorbic acid (C1), some animal species lack the ability to produce L-gulonolactone oxidase and are thus dependent upon a dietary source of vitamin C. Fish are unique among this latter group in that they store a chemically stable form of vitamin C and appear to metabolize this compound differently from other vitamin C-requiring organisms. Ascorbate-2-sulfate (C2) contributes to total body stores of ascorbate, but the commonly used assays for ascorbate concentrations in tissues and body fluids do not generally measure C2...
October 1986: Fish Physiology and Biochemistry
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