Epigenetic effects of ascorbate in the pathomechanism of scurvy and arterial tortuosity disease  Page description

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Details of project

 
Identifier
111031
Type NN
Principal investigator Bánhegyi, Gábor
Title in Hungarian A C-vitamin epigenetikus szerepe a skorbut és a kanyargós artéria szindróma patogenezisében
Title in English Epigenetic effects of ascorbate in the pathomechanism of scurvy and arterial tortuosity disease
Keywords in Hungarian aszkorbát, epigenetika, Fe2+-2-oxoglutarátfüggő dioxigenázok, sejtmag, GLUT10, skorbut, kanyargós artéria szindróma
Keywords in English vitamin C, scurvy, arterial tortuosity syndrome, nucleus, Fe2+-2-oxoglutarate dependent dioxygenases, GLUT10
Discipline
Biological basis of diseases related to the above (Council of Medical and Biological Sciences)50 %
General biochemistry and metabolism (Council of Medical and Biological Sciences)30 %
Ortelius classification: Molecular biology
Cell genetics (Council of Medical and Biological Sciences)20 %
Ortelius classification: Molecular genetics
Panel Molecular and Structural Biology and Biochemistry
Department or equivalent Dept. of Medical Chemistry, Molecular Biology and Pathobiochemistry (Semmelweis University)
Participants Kurucz, Anita Andrea
Németh, Csilla Emese
Nemoda, Zsófia
Varga, Viola
Starting date 2014-04-01
Closing date 2017-09-30
Funding (in million HUF) 19.548
FTE (full time equivalent) 4.30
state running project





 

Final report

 
Results in Hungarian
Megállapítottuk, hogy a kanyargós artéria szindróma patogenezisében kulcsszerepet játszó GLUT10 membránfehérje dehidroaszkorbinsav transzporterként működik, és a fibroblasztok endomembránjaiban található. A GLUT10-deficiens betegekből származó fibroblasztokban alacsonyabb magi aszkorbát szinteket találtunk. Ezzel összhangban, a DNS metilált citozinjainak hidroxilálása is csökkent. Hasonló hatást észleltünk a PPAR-gamma génjében is. Az eredmények felvetik az epigenetikai hatások szerepét a patomechanizmusban.
Results in English
Our results demonstrate that GLUT10, a membrane protein playing a key role in the pathogenesis of arterial tortuosity syndrome, functions as a dehydroascorbic acid transporter and localizes to the endomembranes of fibroblasts. We found lower nuclear ascorbate levels in fibroblasts from patients. In accordance with these observations, decreased hydroxymethylation of methylcytosines were present in the DNA of patients' fibroblasts. Our results suggest the epigenetic effects are integral parts of the pathomechanism.
Full text https://www.otka-palyazat.hu/download.php?type=zarobeszamolo&projektid=111031
Decision
Yes





 

List of publications

 
Margittai É, Enyedi B, Csala M, Geiszt M, Bánhegyi G.: Composition of the redox environment of the endoplasmic reticulum and sources of hydrogen peroxide., Free Radic Biol Med. 2015 Feb 9. pii: S0891-5849(15)00039-8. doi: 10.1016/j.freeradbiomed.2015.01.032. [Epub ahead of print], 2015
Csala M, Kardon T, Legeza B, Lizák B, Mandl J, Margittai É, Puskás F, Száraz P, Szelényi P, Bánhegyi G.: On the role of 4-hydroxynonenal in health and disease., Biochim Biophys Acta. 2015 May;1852(5):826-838., 2015
Bánhegyi G, Benedetti A, Margittai E, Marcolongo P, Fulceri R, Németh CE, Szarka A.: Subcellular compartmentation of ascorbate and its variation in disease states., Biochim Biophys Acta. 2014 Sep;1843(9):1909-16., 2014
Németh CE, Marcolongo P, Gamberucci A, Fulceri R, Benedetti A, Zoppi N, Ritelli M, Chiarelli N, Colombi M, Willaert A, Callewaert BL, Coucke PJ, Gróf P, Nagy SK, Mészáros T, Bánhegyi G, Margittai É.: Glucose transporter type 10-lacking in arterial tortuosity syndrome-facilitates dehydroascorbic acid transport., FEBS Lett. 2016 Jun;590(11):1630-40., 2016
Gamberucci A, Marcolongo P, Németh CE, Zoppi N, Szarka A, Chiarelli N, Hegedűs T, Ritelli M, Carini G, Willaert A, Callewaert BL, Coucke PJ, Benedetti A, Margittai É, Fulceri R, Bánhegyi G, Colombi M.: GLUT10-Lacking in Arterial Tortuosity Syndrome-Is Localized to the Endoplasmic Reticulum of Human Fibroblasts., Int J Mol Sci. 18(8)., 2017




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