Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation

Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation

Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of...

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Main Authors: Kim, Young-Mi, Kim, Jung Hwan, Kwon, Hyuk Min, Lee, Dong Heon, Won, Moo-Ho, Kwon, Young-Guen, Kim, Young-Myeong
Format: Online
Language:English
Published: The Korean Society of Ginseng 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825856/
id pubmed-3825856
recordtype oai_dc
spelling pubmed-38258562013-11-14 Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation Kim, Young-Mi Kim, Jung Hwan Kwon, Hyuk Min Lee, Dong Heon Won, Moo-Ho Kwon, Young-Guen Kim, Young-Myeong Articles Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of human umbilical vein endothelial cells (HUVECs) in a serum-deprived apoptosis model. KRGE protected HUVECs from serum-deprived apoptosis by inhibiting mitochondrial cytochrome c release and caspase-9/-3 activation. This protective effect was significantly higher than that of American ginseng extract. KRGE treatment increased antiapoptotic Bcl-2 and Bcl-XL protein expression and Akt-dependent Bad phosphorylation. Moreover, KRGE prevented serum deprivation-induced subcellular redistribution of these proteins between the mitochondrion and the cytosol, resulting in suppression of mitochondrial cytochrome c release. In addition, KRGE increased nitric oxide (NO) production via Akt-dependent activation of endothelial NO synthase (eNOS), as well as inhibited caspase-9/-3 activities. These increases were reversed by co-treatment of cells with inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) and pre-incubation of cell lysates in dithiothreitol, indicating KRGE induces NO-mediated caspase modification. Indeed, KRGE inhibited caspase-3 activity via S-nitrosylation. These findings suggest that KRGE prevents serum deprivation-induced HUVEC apoptosis via increased Bcl-2 and Bcl-XL protein expression, PI3K/Akt-dependent Bad phosphorylation, and eNOS/NO-mediated S-nitrosylation of caspases. The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases. The Korean Society of Ginseng 2013-10 /pmc/articles/PMC3825856/ /pubmed/24233159 http://dx.doi.org/10.5142/jgr.2013.37.413 Text en Copyright ©2013, The Korean Society of Ginseng http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kim, Young-Mi
Kim, Jung Hwan
Kwon, Hyuk Min
Lee, Dong Heon
Won, Moo-Ho
Kwon, Young-Guen
Kim, Young-Myeong
spellingShingle Kim, Young-Mi
Kim, Jung Hwan
Kwon, Hyuk Min
Lee, Dong Heon
Won, Moo-Ho
Kwon, Young-Guen
Kim, Young-Myeong
Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation
author_facet Kim, Young-Mi
Kim, Jung Hwan
Kwon, Hyuk Min
Lee, Dong Heon
Won, Moo-Ho
Kwon, Young-Guen
Kim, Young-Myeong
author_sort Kim, Young-Mi
title Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation
title_short Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation
title_full Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation
title_fullStr Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation
title_full_unstemmed Korean Red Ginseng protects endothelial cells from serum-deprived apoptosis by regulating Bcl-2 family protein dynamics and caspase S-nitrosylation
title_sort korean red ginseng protects endothelial cells from serum-deprived apoptosis by regulating bcl-2 family protein dynamics and caspase s-nitrosylation
description Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of human umbilical vein endothelial cells (HUVECs) in a serum-deprived apoptosis model. KRGE protected HUVECs from serum-deprived apoptosis by inhibiting mitochondrial cytochrome c release and caspase-9/-3 activation. This protective effect was significantly higher than that of American ginseng extract. KRGE treatment increased antiapoptotic Bcl-2 and Bcl-XL protein expression and Akt-dependent Bad phosphorylation. Moreover, KRGE prevented serum deprivation-induced subcellular redistribution of these proteins between the mitochondrion and the cytosol, resulting in suppression of mitochondrial cytochrome c release. In addition, KRGE increased nitric oxide (NO) production via Akt-dependent activation of endothelial NO synthase (eNOS), as well as inhibited caspase-9/-3 activities. These increases were reversed by co-treatment of cells with inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) and pre-incubation of cell lysates in dithiothreitol, indicating KRGE induces NO-mediated caspase modification. Indeed, KRGE inhibited caspase-3 activity via S-nitrosylation. These findings suggest that KRGE prevents serum deprivation-induced HUVEC apoptosis via increased Bcl-2 and Bcl-XL protein expression, PI3K/Akt-dependent Bad phosphorylation, and eNOS/NO-mediated S-nitrosylation of caspases. The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases.
publisher The Korean Society of Ginseng
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825856/
_version_ 1612026060788989952

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