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dc.contributor.authorStanimirović, Julijana
dc.contributor.authorObradović, Milan M.
dc.contributor.authorPanić, Anastasija
dc.contributor.authorPetrović, Voin
dc.contributor.authorAlavantić, Dragan
dc.contributor.authorMelih, Irena
dc.contributor.authorIsenović, Esma R.
dc.date.accessioned2018-03-10T17:37:38Z
dc.date.available2018-03-10T17:37:38Z
dc.date.issued2018
dc.identifier.urihttp://vinar.vin.bg.ac.rs/handle/123456789/7581
dc.description.abstractIn this study, we assessed whether the disturbed regulation of sodium/potassium-adenosine-triphosphatase (Na+/K+-ATPase) occurs as a consequence of obesity-induced IR in sex-specific manner. We also assessed whether alterations of IRS/PI3K/Akt, ERK1/2, AMPK alpha, and RhoA/ROCK signaling cascades have an important role in this pathology. Female and male Wistar rats (150-200 g, 8 weeks old) were fed a standard laboratory diet or a high-fat (HF) diet (42% fat) for 10 weeks. The activity of hepatic Na+/K+-ATPase and Rho, and the association of IRS-1/p85 were assessed in liver. Furthermore, the protein level of alpha(1) Na+/K+-ATPase in plasma membrane fractions, and protein levels of IRS-1, PI3K-p85, -p110, RhoA, ROCK1, ROCK2, ERK1/2, AMPK alpha, ER alpha, and ER beta in liver lysates were assessed. The expression of hepatic alpha(1) Na+/K+-ATPase mRNA was also analyzed by qRT-PCR. The results show that HF-fed female rats exhibited an increase in hepatic ERK1/2 (p < 0.05) and AMPK alpha (p < 0.05) phosphorylation levels, unchanged level of Na+/K+-ATPase alpha(1) mRNA, decreased level of Na+/K+-ATPase activity (p < 0.05), and decreased alpha(1) Na+/K+-ATPase protein expression (p < 0.01). In liver of HF-fed male rats, results show decreased levels of Na+/K+-ATPase activity (p < 0.01), both protein and mRNA of alpha(1) subunit (p < 0.05), but significant increase in Rho activity (p < 0.05). Our results indicate significant sex differences in alpha(1) Na+/K+-ATPase mRNA expression and activation of ERK1/2, AMPK alpha, and Rho in the liver. Exploring the sex-specific factors and pathways that promote obesity-related diseases may lead to a better understanding of pathogenesis and discovering new therapeutic targets.en
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173033/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41028/RS//
dc.rightsrestrictedAccessen
dc.sourceMolecular and Cellular Biochemistryen
dc.subjectHigh-fat dieten
dc.subjectInsulin resistanceen
dc.subjectLiveren
dc.subjectNa+/K+-ATPaseen
dc.subjectSex differencesen
dc.titleRegulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCKen
dc.typearticleen
dc.citation.volume440
dc.citation.spage77
dc.citation.epage88
dc.identifier.wos000425132100008
dc.identifier.doi10.1007/s11010-017-3157-z
dc.identifier.pmid28819898
dc.identifier.scopus2-s2.0-85027710742


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