17β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis
17 beta-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-alfa and inhibition of erk1/2-mir-221 axis
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Аутори
Panić, AnastasijaStanimirović, Julijana
Obradović, Milan M.
Zafirović, Sonja
Sudar-Milovanović, Emina
Petrović, Nina
Isenović, Esma R.
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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), Ak...t 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.
Извор:
Journal of biological regulators and homeostatic agents, 2018, 32, 6, 1369-1377Колекције
Институција/група
VinčaTY - JOUR AU - Panić, Anastasija AU - Stanimirović, Julijana AU - Obradović, Milan M. AU - Zafirović, Sonja AU - Sudar-Milovanović, Emina AU - Petrović, Nina AU - Isenović, Esma R. PY - 2018 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8013 AB - 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 0.05) 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. T2 - Journal of biological regulators and homeostatic agents T1 - 17β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis VL - 32 IS - 6 SP - 1369 EP - 1377 UR - https://hdl.handle.net/21.15107/rcub_vinar_8013 ER -
@article{ author = "Panić, Anastasija and Stanimirović, Julijana and Obradović, Milan M. and Zafirović, Sonja and Sudar-Milovanović, Emina and Petrović, Nina and Isenović, Esma R.", year = "2018", 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 0.05) 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.", journal = "Journal of biological regulators and homeostatic agents", title = "17β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis", volume = "32", number = "6", pages = "1369-1377", url = "https://hdl.handle.net/21.15107/rcub_vinar_8013" }
Panić, A., Stanimirović, J., Obradović, M. M., Zafirović, S., Sudar-Milovanović, E., Petrović, N.,& Isenović, E. R.. (2018). 17β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis. in Journal of biological regulators and homeostatic agents, 32(6), 1369-1377. https://hdl.handle.net/21.15107/rcub_vinar_8013
Panić A, Stanimirović J, Obradović MM, Zafirović S, Sudar-Milovanović E, Petrović N, Isenović ER. 17β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis. in Journal of biological regulators and homeostatic agents. 2018;32(6):1369-1377. https://hdl.handle.net/21.15107/rcub_vinar_8013 .
Panić, Anastasija, Stanimirović, Julijana, Obradović, Milan M., Zafirović, Sonja, Sudar-Milovanović, Emina, Petrović, Nina, Isenović, Esma R., "17β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis" in Journal of biological regulators and homeostatic agents, 32, no. 6 (2018):1369-1377, https://hdl.handle.net/21.15107/rcub_vinar_8013 .