title: Heterozygous connexin 50 mutation affects metabolic syndrome attributes in spontaneously hypertensive rat.
abstract: BACKGROUND
  Several members of connexin family of transmembrane proteins were previously implicated in distinct metabolic conditions. In this study we aimed to determine the effects of complete and heterozygous form of connexin50 gene (Gja8) mutation L7Q on metabolic profile and oxidative stress parameters in spontaneously hypertensive inbred rat strain (SHR).
  
  
  METHODS
  Adult, standard chow-fed male rats of SHR, heterozygous SHR-Dca+/- and SHR-Dca-/- coisogenic strains were used. At the age of 4 months, dexamethasone (2.6 μg/ml) was administered in the drinking water for three days. The lipidemic profile (cholesterol and triacylglycerol concentration in 20 lipoprotein fractions, chylomicron, VLDL, LDL and HDL particle sizes) together with 33 cytokines and hormones in serum and several oxidative stress parameters in plasma, liver, kidney and heart were assessed.
  
  
  RESULTS
  SHR and SHR-Dca-/- rats had similar concentrations of triacylglycerols and cholesterol in all major lipoprotein fractions. The heterozygotes reached significantly highest levels of total (SHR-Dca+/-: 51.3 ± 7.2 vs. SHR: 34.5 ± 2.4 and SHR-Dca-/-: 34.4 ± 2.5 mg/dl, p = 0.026), chylomicron and VLDL triacylglycerols. The heterozygotes showed significantly lowest values of HDL cholesterol (40.9 ± 2.3 mg/dl) compared both to SHR (51.8 ± 2.2 mg/dl) and SHR-Dca-/- (48.6 ± 2.7 mg/dl). Total and LDL cholesterol in SHR-Dca+/- was lower compared to SHR. Glucose tolerance was improved and insulin concentrations were lowest in SHR-Dca-/- (1.11 ± 0.20 pg/ml) in comparison with both SHR (2.32 ± 0.49 pg/ml) and SHR-Dca+/- (3.04 ± 0.21 pg/ml). The heterozygous rats showed profile suggestive of increased oxidative stress as well as highest serum concentrations of several pro-inflammatory cytokines including interleukins 6, 12, 17, 18 and tumor necrosis factor alpha.
  
  
  CONCLUSIONS
  Our results demonstrate that connexin50 mutation in heterozygous state affects significantly the lipid profile and the oxidative stress parameters in the spontaneously hypertensive rat strain.
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic. ondrej.seda@lf1.cuni.cz.|Division BIOCEV, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, Laboratory of Rat Models of Metabolic Disorders, Vídeňská 1083, 142 20, Prague 4, Czech Republic. ondrej.seda@lf1.cuni.cz.
authors.forename: Ondřej
authors.identifier: http://orcid.org/0000-0001-8498-5895
authors.initials: O
authors.lastname: Šeda
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic.
authors.forename: Drahomíra
authors.initials: D
authors.lastname: Křenová
authors.affiliation: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague 4, Czech Republic.
authors.forename: Olena
authors.initials: O
authors.lastname: Oliyarnyk
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic.|Division BIOCEV, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, Laboratory of Rat Models of Metabolic Disorders, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Šedová
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Krupková
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Liška
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Chylíková
authors.affiliation: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague 4, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kazdová
authors.affiliation: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D017630:Connexins / Q000235:genetics*; D016207:Cytokines / Q000097:blood; D006579:Heterozygote; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D014280:Triglycerides / Q000097:blood; D000099264:Connexin 50
chemical_list: D002784:Cholesterol; D017630:Connexins; D016207:Cytokines; D007328:Insulin; D014280:Triglycerides; D000099264:Connexin 50
keywords: Animal models; Connexin; Lipoprotein; Metabolic syndrome; Oxidative stress