17ß-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis.
J Biol Regul Homeost Agents
; 32(6): 1369-1377, 2018.
Article
em En
| MEDLINE
| ID: mdl-30574741
ABSTRACT
17ß-Estradiol (E2) is known to negatively regulate inducible nitric oxide (NO) synthase (iNOS) expression via estrogen receptor alpha (ER-α) activation in aortic vascular smooth muscle cells.Therefore, we sought to determine whether E2 can inhibit iNOS in vivo in hepatic tissue via the activation of ER-α and whether extracellular signal-regulated kinases 1/2 (ERK1/2)-miR-221 axis is involved in this process. Male Wistar rats were treated with a bolus injection of E2 intraperitoneally (40 µg/kg), and 24 hours after treatment the animals were sacrificed and the livers excised. The protein levels of iNOS, p50 and p65 subunits of nuclear factor κB (NFκB), ERα, ERK1/2 and protein kinase B (Akt), as well as the association of ERα/Src in liver lysates were assessed by Western blot. The expression of hepatic miR-221 was analyzed by qRT-PCR. Results show that E2 reduced hepatic iNOS protein expression (p less than 0.01), the protein level of ERα (p less than 0.05), ERK1/2 (p less than 0.05), Akt phosphorylation (p less than 0.001) and miR-221 expression (p less than 0.05). In contrast, hepatic ERα/Src kinase association level (p less than 0.05) increased after E2 treatment. Our results indicate that E2 inhibits hepatic iNOS via molecular mechanisms involving the activation of the ER-α and inhibition of ERK1/2-miR-221 axis.
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Base de dados:
MEDLINE
Assunto principal:
Sistema de Sinalização das MAP Quinases
/
MicroRNAs
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Receptor alfa de Estrogênio
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Estradiol
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Óxido Nítrico Sintase Tipo II
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Fígado
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article