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Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK
dc.contributor.author | Stanimirović, Julijana | |
dc.contributor.author | Obradović, Milan M. | |
dc.contributor.author | Panić, Anastasija | |
dc.contributor.author | Petrović, Voin | |
dc.contributor.author | Alavantić, Dragan | |
dc.contributor.author | Melih, Irena | |
dc.contributor.author | Isenović, Esma R. | |
dc.date.accessioned | 2018-03-10T17:37:38Z | |
dc.date.available | 2090-01-01 | |
dc.date.issued | 2018 | |
dc.identifier.issn | 0300-8177 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/7581 | |
dc.description.abstract | In 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.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173033/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41028/RS// | |
dc.rights | restrictedAccess | en |
dc.source | Molecular and Cellular Biochemistry | en |
dc.subject | High-fat diet | en |
dc.subject | Insulin resistance | en |
dc.subject | Liver | en |
dc.subject | Na+/K+-ATPase | en |
dc.subject | Sex differences | en |
dc.title | Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK | en |
dc.type | article | en |
dc.rights.license | ARR | |
dc.citation.volume | 440 | |
dc.citation.spage | 77 | |
dc.citation.epage | 88 | |
dc.identifier.wos | 000425132100008 | |
dc.identifier.doi | 10.1007/s11010-017-3157-z | |
dc.citation.rank | M23 | |
dc.identifier.pmid | 28819898 | |
dc.type.version | publishedVersion | |
dc.identifier.scopus | 2-s2.0-85027710742 |