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NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

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@article{e3ee2e25a5ca4054a5fe57724a85ceb0,
title = "NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries",
abstract = "Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) receptor upregulation and activation of NF-kappaB were studied at functional contraction (in vitro myograph), mRNA (real-time PCR), and protein (Western blot and immunocytochemistry) levels during organ culture of rat mesenteric arteries. Organ culture of the artery segments induced a time-dependent strong contractile response to sarafotoxin 6c in parallel with enhanced expression of ET(B) receptor mRNA and protein in the SMC. Western blot experiments demonstrated that phosphorylation of NF-kappaB p65 was time-dependently induced during organ culture starting at 1h. In addition, cytoplasmic IkB degradation occurred in parallel with nuclear NF-kappaB accumulation following organ culture. The enhanced expression of ET(B) receptor protein was apparent at 3h in the SMC and while enhanced ET(B) receptor-mediated contractions occurred first at 12h. The specific IkappaB inhibitors, IMD-0354 (N-(3,5-Bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide) and Wedelolactone (7-Methoxy-5,11,12-trihydroxycoumestan), abolished the organ culture induced ET(B) receptor upregulation. The intracellular NF-kappaB pathway is involved in the process of induced expression of vascular SMC ET(B) receptors.",
author = "Jian-Pu Zheng and Yaping Zhang and Lars Edvinsson and Tord Hjalt and Cang-Bao Xu",
note = "Copyright 2010 Elsevier B.V. All rights reserved.",
year = "2010",
month = jul,
day = "10",
doi = "10.1016/j.ejphar.2010.04.006",
language = "English",
volume = "637",
pages = "148--54",
journal = "European Journal of Clinical Pharmacology",
issn = "0031-6970",
publisher = "Springer",
number = "1-3",

}

RIS

TY - JOUR

T1 - NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

AU - Zheng, Jian-Pu

AU - Zhang, Yaping

AU - Edvinsson, Lars

AU - Hjalt, Tord

AU - Xu, Cang-Bao

N1 - Copyright 2010 Elsevier B.V. All rights reserved.

PY - 2010/7/10

Y1 - 2010/7/10

N2 - Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) receptor upregulation and activation of NF-kappaB were studied at functional contraction (in vitro myograph), mRNA (real-time PCR), and protein (Western blot and immunocytochemistry) levels during organ culture of rat mesenteric arteries. Organ culture of the artery segments induced a time-dependent strong contractile response to sarafotoxin 6c in parallel with enhanced expression of ET(B) receptor mRNA and protein in the SMC. Western blot experiments demonstrated that phosphorylation of NF-kappaB p65 was time-dependently induced during organ culture starting at 1h. In addition, cytoplasmic IkB degradation occurred in parallel with nuclear NF-kappaB accumulation following organ culture. The enhanced expression of ET(B) receptor protein was apparent at 3h in the SMC and while enhanced ET(B) receptor-mediated contractions occurred first at 12h. The specific IkappaB inhibitors, IMD-0354 (N-(3,5-Bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide) and Wedelolactone (7-Methoxy-5,11,12-trihydroxycoumestan), abolished the organ culture induced ET(B) receptor upregulation. The intracellular NF-kappaB pathway is involved in the process of induced expression of vascular SMC ET(B) receptors.

AB - Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) receptor upregulation and activation of NF-kappaB were studied at functional contraction (in vitro myograph), mRNA (real-time PCR), and protein (Western blot and immunocytochemistry) levels during organ culture of rat mesenteric arteries. Organ culture of the artery segments induced a time-dependent strong contractile response to sarafotoxin 6c in parallel with enhanced expression of ET(B) receptor mRNA and protein in the SMC. Western blot experiments demonstrated that phosphorylation of NF-kappaB p65 was time-dependently induced during organ culture starting at 1h. In addition, cytoplasmic IkB degradation occurred in parallel with nuclear NF-kappaB accumulation following organ culture. The enhanced expression of ET(B) receptor protein was apparent at 3h in the SMC and while enhanced ET(B) receptor-mediated contractions occurred first at 12h. The specific IkappaB inhibitors, IMD-0354 (N-(3,5-Bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide) and Wedelolactone (7-Methoxy-5,11,12-trihydroxycoumestan), abolished the organ culture induced ET(B) receptor upregulation. The intracellular NF-kappaB pathway is involved in the process of induced expression of vascular SMC ET(B) receptors.

U2 - 10.1016/j.ejphar.2010.04.006

DO - 10.1016/j.ejphar.2010.04.006

M3 - Journal article

C2 - 20399772

VL - 637

SP - 148

EP - 154

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

SN - 0031-6970

IS - 1-3

ER -

ID: 32311384