Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Genetic Variation in Renal Expression of Folate Receptor 1 (Folr1) Gene Predisposes Spontaneously Hypertensive Rats to Metabolic Syndrome

M. Pravenec, V. Kožich, J. Krijt, J. Sokolová, V. Zídek, V. Landa, P. Mlejnek, J. Šilhavý, M. Šimáková, V. Škop, J. Trnovská, L. Kazdová, T. Kajiya, J. Wang, TW. Kurtz,

. 2016 ; 67 (2) : 335-41. [pub] 20151214

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc16020091

Metabolism of homocysteine and other sulfur amino acids is closely associated with metabolism of folates. In this study, we analyzed the possible role of folates and sulfur amino acids in the development of features of the metabolic syndrome in the BXH/HXB recombinant inbred strains derived from the spontaneously hypertensive rat (SHR) and Brown Norway progenitors. We mapped a quantitative trait locus for cysteine concentrations to a region of chromosome 1 that contains a cis-acting expression quantitative trait locus regulating mRNA levels of folate receptor 1 (Folr1) in the kidney. Sequence analysis revealed a deletion variant in the Folr1 promoter region of the SHR. Transfection studies demonstrated that the SHR-promoter region of Folr1 is less effective in driving luciferase reporter gene expression than the Brown Norway promoter region of Folr1. Results in the SHR.BN-chr.1 congenic strain confirmed that the SHR variant in Folr1 cosegregates with markedly reduced renal expression of Folr1 and renal folate reabsorption, decreased serum levels of folate, increased serum levels of cysteine and homocysteine, increased adiposity, ectopic fat accumulation in liver and muscle, reduced muscle insulin sensitivity, and increased blood pressure. Transgenic rescue experiments performed by expressing a Folr1 transgene in the SHR ameliorated most of the metabolic disturbances. These findings are consistent with the hypothesis that inherited variation in the expression of Folr1 in the kidney influences the development of the metabolic syndrome and constitutes a previously unrecognized genetic mechanism that may contribute to increased risk for diabetes mellitus and cardiovascular disease.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc16020091
003      
CZ-PrNML
005      
20250618144158.0
007      
ta
008      
160722s2016 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1161/HYPERTENSIONAHA.115.06158 $2 doi
024    7_
$a 10.1161/HYPERTENSIONAHA.115.06158 $2 doi
035    __
$a (PubMed)26667416
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Pravenec, Michal $u Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
245    10
$a Genetic Variation in Renal Expression of Folate Receptor 1 (Folr1) Gene Predisposes Spontaneously Hypertensive Rats to Metabolic Syndrome / $c M. Pravenec, V. Kožich, J. Krijt, J. Sokolová, V. Zídek, V. Landa, P. Mlejnek, J. Šilhavý, M. Šimáková, V. Škop, J. Trnovská, L. Kazdová, T. Kajiya, J. Wang, TW. Kurtz,
520    9_
$a Metabolism of homocysteine and other sulfur amino acids is closely associated with metabolism of folates. In this study, we analyzed the possible role of folates and sulfur amino acids in the development of features of the metabolic syndrome in the BXH/HXB recombinant inbred strains derived from the spontaneously hypertensive rat (SHR) and Brown Norway progenitors. We mapped a quantitative trait locus for cysteine concentrations to a region of chromosome 1 that contains a cis-acting expression quantitative trait locus regulating mRNA levels of folate receptor 1 (Folr1) in the kidney. Sequence analysis revealed a deletion variant in the Folr1 promoter region of the SHR. Transfection studies demonstrated that the SHR-promoter region of Folr1 is less effective in driving luciferase reporter gene expression than the Brown Norway promoter region of Folr1. Results in the SHR.BN-chr.1 congenic strain confirmed that the SHR variant in Folr1 cosegregates with markedly reduced renal expression of Folr1 and renal folate reabsorption, decreased serum levels of folate, increased serum levels of cysteine and homocysteine, increased adiposity, ectopic fat accumulation in liver and muscle, reduced muscle insulin sensitivity, and increased blood pressure. Transgenic rescue experiments performed by expressing a Folr1 transgene in the SHR ameliorated most of the metabolic disturbances. These findings are consistent with the hypothesis that inherited variation in the expression of Folr1 in the kidney influences the development of the metabolic syndrome and constitutes a previously unrecognized genetic mechanism that may contribute to increased risk for diabetes mellitus and cardiovascular disease.
650    _2
$a zvířata $7 D000818
650    _2
$a krevní tlak $x fyziologie $7 D001794
650    _2
$a folátový receptor 1 $x biosyntéza $x genetika $7 D058975
650    12
$a regulace genové exprese $7 D005786
650    12
$a genetická predispozice k nemoci $7 D020022
650    _2
$a genetická variace $7 D014644
650    _2
$a hypertenze $x komplikace $x genetika $x metabolismus $7 D006973
650    _2
$a ledviny $x metabolismus $7 D007668
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a metabolický syndrom $x etiologie $x genetika $x metabolismus $7 D024821
650    _2
$a RNA $x genetika $7 D012313
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a potkani inbrední BN $7 D011914
650    _2
$a potkani inbrední SHR $7 D011918
650    _2
$a kvantitativní polymerázová řetězová reakce $7 D060888
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Kožich, Viktor $u Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
700    1_
$a Krijt, Jakub $u Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
700    1_
$a Sokolová, Jitka
700    1_
$a Zídek, Václav $u From the Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Landa, Vladimír $u From the Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Mlejnek, Petr $u From the Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Šilhavý, Jan $u From the Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Šimáková, Miroslava $u From the Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Škop, Vojtěch $u Center of Experimental Medicine, Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
700    1_
$a Trnovská, Jaroslava $u Center of Experimental Medicine, Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
700    1_
$a Kazdová, Ludmila, $d 1938-2025 $u Center of Experimental Medicine, Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic $7 xx0053119
700    1_
$a Kajiya, Takashi $u Department of Laboratory Medicine, University of California, San Francisco
700    1_
$a Wang, Jiaming $u Department of Laboratory Medicine, University of California, San Francisco
700    1_
$a Kurtz, Theodore W $u Department of Laboratory Medicine, University of California, San Francisco
773    0_
$w MED00002089 $t Hypertension $x 1524-4563 $g Roč. 67, č. 2 (2016), s. 335-41
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26667416 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20160722 $b ABA008
991    __
$a 20250618144149 $b ABA008
999    __
$a ok $b bmc $g 1154761 $s 944619
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 67 $c 2 $d 335-41 $e 20151214 $i 1524-4563 $m Hypertension $n Hypertension $x MED00002089
LZP    __
$a Pubmed-20160722

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace