RGD Reference Report - Estradiol-mediated regulation of hepatic iNOS in obese rats: Impact of Src, ERK1/2, AMPKα, and miR-221. - Rat Genome Database

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Estradiol-mediated regulation of hepatic iNOS in obese rats: Impact of Src, ERK1/2, AMPKα, and miR-221.

Authors: Panic, Anastasija  Stanimirovic, Julijana  Obradovic, Milan  Sudar-Milovanovic, Emina  Perovic, Milan  Lackovic, Milena  Petrovic, Nina  Isenovic, Esma R 
Citation: Panic A, etal., Biotechnol Appl Biochem. 2018 Nov;65(6):797-806. doi: 10.1002/bab.1680. Epub 2018 Aug 6.
RGD ID: 18337276
Pubmed: PMID:29957877   (View Abstract at PubMed)
DOI: DOI:10.1002/bab.1680   (Journal Full-text)


PURPOSE: This study aimed to investigate in vivo effects of estradiol on the regulation of hepatic inducible nitric oxide synthase (iNOS) expression in the high fat (HF) diet-induced obesity. Also, we aimed to investigate whether activation of the extracellular signal-regulated kinase (ERK1/2), adenosine monophosphate-activated protein kinase (AMPK), Src kinase, and miR-221 is involved in estradiol-mediated regulation of iNOS in the liver of obese male Wistar rats. Male Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. Half of HF rats were treated with estradiol intraperitoneally (40 μg/kg), whereas the other half were placebo-treated 24 H before euthanasia. Results show that estradiol treatment of HF rats decreased hepatic iNOS mRNA (P < 0.05) and protein expression (P < 0.01), the protein levels of p65 subunit of nuclear factor κB (P < 0.05) and ERα (P < 0.05), ERK1/2 phosphorylation (P < 0.001), and ERα/Src kinase association (P < 0.05). By contrast, hepatic Src protein level (P < 0.05), AMPKα phosphorylation (P < 0.05), and miR-221 expression (P < 0.05) were increased in HF rats after estradiol treatment. Our results indicate that estradiol in vivo regulates hepatic iNOS expression in obese rats via molecular mechanisms involving ERK1/2, AMPK, Src, and miR-221 signaling.




Biological Process

  
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Species
Term
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Evidence
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Original Reference(s)
Mir221Ratresponse to estradiol  IEP  RGD 


Genes (Rattus norvegicus)
Mir221  (microRNA 221)