Isoproterenol Inhibits Angiotensin II-Stimulated Proliferation and Reactive Oxygen Species Production in Vascular Smooth Muscle Cells through Heme Oxygenase-1

Kim, Jung Eun; Kang, Young Jin; Lee, Kwang Youn; Choi, Hyoung Chul

doi:10.1248/bpb.32.1047

Cited by 26 publications

(17 citation statements)

References 27 publications

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“…Duckers et al have demonstrated that CO induces the expression of the cdk-2 inhibitor p21 WAF1/CIP1 , suggesting that CO may block cdk-2 activity via multiple mechanisms to inhibit VSMC proliferation [8] . In addition, Ang II induces ROS production through the ERK1/2 pathway Li XC et al Acta Pharmacologica Sinica npg in VSMCs [39] . Oxidants, including ROS, are signals involved in the regulation of cell proliferation [40] .…”

Section: Discussionmentioning

confidence: 99%

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Tong

Zhang

et al. 2010

Acta Pharmacol Sin

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Aim:To explore the effect of neferine on angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. Methods: Human umbilical vein smooth muscle cells (HUVSMCs) were used. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. Heme oxygenase (HO)-1 protein expression was tested by Western blot analysis. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation was determined by using immunoblotting. Results: Pre-incubation of HUVSMCs with neferine (0.1, 0.5, 1.0, and 5.0 µmol/L) significantly inhibited Ang II-induced cell proliferation in a concentration-dependent manner and neferine 5.0 µmol/L increased HO-1 expression by 259% compared with control. The antiproliferative effect of neferine was significantly attenuated by coapplication of zinc protoporphyrin IX (ZnPP IX, an HO-1 inhibitor) with neferine. Ang II-enhanced ERK1/2 phosphorylation was markedly reversed by neferine. By inhibiting HO-1 activity with ZnPP IX, the inhibitive effect of neferine on ERK1/2 phosphorylation was significantly attenuated. Cobalt-protoporphyrin (CoPP), an HO-1 inducer, significantly decreased Ang II-induced ERK1/2 phosphorylation and inhibited Ang II-induced cell proliferation. The ERK1/2 pathway inhibitor PD98059 significantly blocked Ang II-enhanced ERK1/2 phosphorylation and inhibited cell proliferation. Conclusion: These findings suggest that neferine can inhibit Ang II-induced HUVSMC proliferation by upregulating HO-1, leading to the at least partial downregulation of ERK1/2 phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Tong

Zhang

et al. 2010

Acta Pharmacol Sin

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“…Indeed, direct exposure to CO suppresses restenosis after carotid balloon injury in rats and mice, and this protective effect is closely associated with a strong inhibition of vascular inflammation and VSMC proliferation (132,195). This effect was elicited by the generation of cGMP, the activation of p38 MAPK, and expression of the cell cycle inhibitor p21 (195).…”

Section: Restenosis and Vasculopathymentioning

confidence: 99%

Heme Oxygenase in the Regulation of Vascular Biology: From Molecular Mechanisms to Therapeutic Opportunities

Kim

Pae

Park

et al. 2011

Antioxidants & Redox Signaling

190

173

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Heme oxygenases (HOs) are the rate-limiting enzymes in the catabolism of heme into biliverdin, free iron, and carbon monoxide. Two genetically distinct isoforms of HO have been characterized: an inducible form, HO-1, and a constitutively expressed form, HO-2. HO-1 is a kind of stress protein, and thus regarded as a sensitive and reliable indicator of cellular oxidative stress. The HO system acts as potent antioxidants, protects endothelial cells from apoptosis, is involved in regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in angiogenesis and vasculogenesis. Endothelial integrity and activity are thought to occupy the central position in the pathogenesis of cardiovascular diseases. Cardiovascular disease risk conditions converge in the contribution to oxidative stress. The oxidative stress leads to endothelial and vascular smooth muscle cell dysfunction with increases in vessel tone, cell growth, and gene expression that create a pro-thrombotic= pro-inflammatory environment. Subsequent formation, progression, and obstruction of atherosclerotic plaque may result in myocardial infarction, stroke, and cardiovascular death. This background provides the rationale for exploring the potential therapeutic role for HO system in the amelioration of vascular inflammation and prevention of adverse cardiovascular outcomes. Antioxid. Redox Signal. 14, 137-167.

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“…10) These can be triggered by various extracellular mitogenic stimuli, such as PDGF-BB, that activate a variety of signaling events involved in the regulation of cell growth and division. [18][19][20] In addition, an association between PDGF and VSMC proliferation has been demonstrated in animal experiments, which showed increases in PDGF-BB after arterial injury were correlated with neointimal cellular proliferation. 21,22) To determine whether KTJ2242 (Fig.…”

Section: Methodsmentioning

confidence: 95%

Potent Inhibition of Platelet-Derived Growth Factor-Stimulated Rat Aortic Vascular Smooth Muscle Cell Cycle and Proliferation by (2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-1-one, a Newly Synthesized Benzylideneacetophenone Derivative

Kim

Han

Jung

et al. 2011

JOURNAL OF HEALTH SCIENCE

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One of the principal regulators of mitogenesis in vascular smooth muscle cells (VSMCs) is platelet-derived growth factor-BB (PDGF-BB). An increase of PDGF-BB expression has been observed in atherosclerotic lesions. The aim of this study was to elucidate the effects and molecular mechanism of (2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-1-one (KTJ2242), a newly synthesized benzylideneacetophenone derivative, on PDGF-BB-stimulated rat aortic VSMCs. KTJ2242 induced accumulation of cells in the G1 phase of the cell cycle of VSMCs. We observed that KTJ2242 inhibited PDGF-BB-stimulated [ 3 H]-thymidine incorporation into the DNA of VSMCs, and the cell number was significantly reduced in a concentration-dependent manner. # These two authors contributed equally to this work. Also, we observed that KTJ2242 decreased PDGF-BB-stimulated extracellular-regulated kinase 1 and 2 (ERK1/2) and Akt phosphorylation. These results suggest the possibility that KTJ2242 may be a potential agent with which to control vascular disorders and its antiproliferative mechanism may be mediated through partial Akt and ERK1/2-dependent signaling pathways.

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Isoproterenol Inhibits Angiotensin II-Stimulated Proliferation and Reactive Oxygen Species Production in Vascular Smooth Muscle Cells through Heme Oxygenase-1

Cited by 26 publications

References 27 publications

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Heme Oxygenase in the Regulation of Vascular Biology: From Molecular Mechanisms to Therapeutic Opportunities

Potent Inhibition of Platelet-Derived Growth Factor-Stimulated Rat Aortic Vascular Smooth Muscle Cell Cycle and Proliferation by (2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-1-one, a Newly Synthesized Benzylideneacetophenone Derivative

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