Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.

Nitric oxide (NO) produced by endothelial nitric-oxide synthase (eNOS) has antithrombotic and antiatherosclerotic properties in the vasculature. Previously, we demonstrated that saponins derived from the roots of Platycodon grandiflorum (CKS) inhibited the tumor necrosis factor-alpha-induced express...

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Autori principali: Kim, H, Hien, T, Han, E, Chung, Y, Jeong, H
Natura: Journal article
Lingua:English
Pubblicazione: 2010
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author Kim, H
Hien, T
Han, E
Chung, Y
Jeong, H
author_facet Kim, H
Hien, T
Han, E
Chung, Y
Jeong, H
author_sort Kim, H
collection OXFORD
description Nitric oxide (NO) produced by endothelial nitric-oxide synthase (eNOS) has antithrombotic and antiatherosclerotic properties in the vasculature. Previously, we demonstrated that saponins derived from the roots of Platycodon grandiflorum (CKS) inhibited the tumor necrosis factor-alpha-induced expression of adhesion molecules in human endothelial cells. In this study, we found that CKS increased eNOS phosphorylation and NO production in human endothelial cells. Treatment with CKS increased the phosphorylation of Akt, p38/MAPK, AMP-activated protein kinase (AMPK), and calmodulin-dependent protein kinase II (CaMK II) leading to increased NO production in human endothelial cells. Moreover, inhibitors of Akt (LY294002), p38/MAPK (SB203580), AMPK (compound C), and CaMK II (W7) failed to suppress CKS-induced eNOS phosphorylation. In addition, CKS-induced eNOS phosphorylation was inhibited by the overexpression of a dominant-negative mutant form of AMPK (DN-AMPK). Taken together, these results indicate that CKS stimulates eNOS phosphorylation and NO production via the activation of PI3K/Akt, p38/MAPK, AMPK, and CaMK II.
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spelling oxford-uuid:0addc602-3911-40ee-8341-d47b9bd7723e2022-03-26T09:26:20ZMolecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0addc602-3911-40ee-8341-d47b9bd7723eEnglishSymplectic Elements at Oxford2010Kim, HHien, THan, EChung, YJeong, HNitric oxide (NO) produced by endothelial nitric-oxide synthase (eNOS) has antithrombotic and antiatherosclerotic properties in the vasculature. Previously, we demonstrated that saponins derived from the roots of Platycodon grandiflorum (CKS) inhibited the tumor necrosis factor-alpha-induced expression of adhesion molecules in human endothelial cells. In this study, we found that CKS increased eNOS phosphorylation and NO production in human endothelial cells. Treatment with CKS increased the phosphorylation of Akt, p38/MAPK, AMP-activated protein kinase (AMPK), and calmodulin-dependent protein kinase II (CaMK II) leading to increased NO production in human endothelial cells. Moreover, inhibitors of Akt (LY294002), p38/MAPK (SB203580), AMPK (compound C), and CaMK II (W7) failed to suppress CKS-induced eNOS phosphorylation. In addition, CKS-induced eNOS phosphorylation was inhibited by the overexpression of a dominant-negative mutant form of AMPK (DN-AMPK). Taken together, these results indicate that CKS stimulates eNOS phosphorylation and NO production via the activation of PI3K/Akt, p38/MAPK, AMPK, and CaMK II.
spellingShingle Kim, H
Hien, T
Han, E
Chung, Y
Jeong, H
Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.
title Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.
title_full Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.
title_fullStr Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.
title_full_unstemmed Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.
title_short Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins.
title_sort molecular mechanism of endothelial nitric oxide synthase activation by platycodon grandiflorum root derived saponins
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