Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK
| Autor: | Anastasija Panic, Esma R. Isenovic, Dragan Alavantić, Irena Melih, Milan Obradovic, Julijana Stanimirovic, Voin Petrovic |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty RHOA Clinical chemistry Sodium Clinical Biochemistry chemistry.chemical_element 03 medical and health sciences Internal medicine Sex differences medicine ROCK1 ROCK2 Na+/K+-ATPase Molecular Biology Protein kinase B biology AMPK Insulin resistance Cell Biology General Medicine High-fat diet 030104 developmental biology Endocrinology Liver chemistry biology.protein |
| Zdroj: | Molecular and Cellular Biochemistry |
| ISSN: | 1573-4919 0300-8177 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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