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- Xu, Cang-Bao, et al.
(författare)
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Lipid soluble smoke particles up-regulate vascular smooth muscle ETB receptors via activation of mitogen activating protein kinases and NF-kappaB pathways.
- 2008
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-0929 .- 1096-6080. ; 106:2, s. 546-555
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Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoke is a strong risk factor for cardiovascular disease. However, the underlying molecular mechanisms that lead to cigarette smoke-associated cardiovascular disease remain elusive. With functional and molecular methods, we demonstrate for the first time that lipid soluble cigarette smoke particles (DSP) increased the expression of endothelin type B (ET(B)) receptors in arterial smooth muscle cells. The increased ET(B) receptors in arterial smooth muscle cells was documented as enhanced contractility (sensitive myograph technique), elevated levels of ET(B) receptor mRNA (quantitative real-time PCR) and protein expressions (immunohistochemistry and Western blotting). Intracellular signalling was studied with Western blotting and phosphoELISA; this revealed that DSP induced extracellular-regulated protein kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) phosphorylation within 3 hours. Blocking ERK1/2, p38 or NF-kappaB activation by their specific inhibitors significantly attenuated the DSP-induced up-regulation of ET(B) receptor-mediated contraction and both ET(B) receptor mRNA and protein expression. In addition, dexamethasone abolished the DSP-induced up-regulation of ET(B) receptor-mediated contraction. In conclusion, up-regulation of ET(B) receptors by DSP in arterial smooth muscle cells involves activation of mitogen activating protein kinases (ERK1/2 and p38) and the downstream transcriptional factor NF-kappaB pathways.
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| 2. |
- Xu, Cang-Bao, et al.
(författare)
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Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression.
- 2014
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 60:1, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- Vasoconstrictive endothelin type B (ETB) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ETB receptor expression and if extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are involved in this process. Rat mesenteric artery segments were organ cultured in the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and 2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ETB receptor expression was studied using a sensitive myograph, real-time PCR and Western blot. LDL (11, 22 and 44mg protein/L) concentration-dependently induced upregulation of vasoconstrictive ETB receptor expression with increase in the receptor-mediated vasoconstriction, elevated levels of the ETB receptor mRNA and protein expressions, and activation of ERK1/2 and p38 MAPK. Blockage of ERK1/2 and p38 MAPK signal pathways using MEK1/2 inhibitors (PD98059 and U0126) or p38 inhibitors (SB203580 and SB239063) significantly abolished the LDL-induced upregulation of vasoconstrictive ETB receptor expression. Actinomycin D (general transcriptional inhibitor) almost completely inhibited the LDL effects. In conclusion, LDL induces upregulation of vasoconstrictive ETB receptor expression through activation of ERK1/2 and p38 MAPK signal pathway-dependent transcriptional mechanisms.
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| 3. |
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| 4. |
- Zheng, Jian-Pu, et al.
(författare)
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NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries.
- 2010
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; Mar 4, s. 148-154
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Tidskriftsartikel (refereegranskat)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 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.
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