Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK
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2018
Contributors
Stanimirović, JulijanaObradović, Milan M.
Panić, Anastasija
Petrović, Voin
Alavantić, Dragan
Melih, Irena
Isenović, Esma R.
Article (Published version)
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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.
Keywords:
High-fat diet / Insulin resistance / Liver / Na+/K+-ATPase / Sex differencesSource:
Molecular and Cellular Biochemistry, 2018, 440, 77-88Funding / projects:
- Hormonal regulation of expression and activity of the nitric oxide synthase and sodium-potassium pump in experimental models of insulin resistance, diabetes and cardiovascular disorders (RS-173033)
- An integral study to identify the regional genetic and environmental risk factors for the common noncommunicable diseases in the human population of Serbia - INGEMA_S (RS-41028)
DOI: 10.1007/s11010-017-3157-z
ISSN: 0300-8177
PubMed: 28819898
WoS: 000425132100008
Scopus: 2-s2.0-85027710742
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VinčaTY - JOUR PY - 2018 UR - https://vinar.vin.bg.ac.rs/handle/123456789/7581 AB - 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. T2 - Molecular and Cellular Biochemistry T1 - Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK VL - 440 SP - 77 EP - 88 DO - 10.1007/s11010-017-3157-z ER -
@article{ year = "2018", 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.", journal = "Molecular and Cellular Biochemistry", title = "Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK", volume = "440", pages = "77-88", doi = "10.1007/s11010-017-3157-z" }
(2018). Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK. in Molecular and Cellular Biochemistry, 440, 77-88. https://doi.org/10.1007/s11010-017-3157-z
Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK. in Molecular and Cellular Biochemistry. 2018;440:77-88. doi:10.1007/s11010-017-3157-z .
"Regulation of hepatic Na+/K+-ATPase in obese female and male rats: involvement of ERK1/2, AMPK, and Rho/ROCK" in Molecular and Cellular Biochemistry, 440 (2018):77-88, https://doi.org/10.1007/s11010-017-3157-z . .