17 β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis.

17β-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. 2018 Nov-Dec;32(6):1369-1377 Authors: Panic A, Stanimirovic J, Obradovic M, Zafirovic S, Sudar-Milovanovic E, Petrovic N, Isenovic ER Abstract 17β-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...
Source: Journal of Biological Regulators and Homeostatic Agents - Category: Biomedical Science Tags: J Biol Regul Homeost Agents Source Type: research