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

Young Mi Kim, Jung Hwan Kim, Hyuk Min Kwon, Dong Heon Lee, Moo Ho Won, Young Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)413-424
Number of pages12
JournalJournal of Ginseng Research
Volume37
Issue number4
DOIs
Publication statusPublished - 2013 Oct

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Panax
Family Relations
Endothelial cells
Caspases
bcl-X Protein
Endothelial Cells
Apoptosis
Nitric Oxide
Phosphorylation
Caspase 9
Phosphatidylinositols
Cytochromes c
Serum
Nitric Oxide Synthase
Proteins
Phosphotransferases
Chemical activation
Cells
Cardiovascular system
Mitochondria

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Complementary and alternative medicine

Cite this

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. In: Journal of Ginseng Research. 2013 ; Vol. 37, No. 4. pp. 413-424.
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abstract = "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.",
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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.

In: Journal of Ginseng Research, Vol. 37, No. 4, 10.2013, p. 413-424.

Research output: Contribution to journalArticle

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AU - Kim, Young Mi

AU - Kim, Jung Hwan

AU - Kwon, Hyuk Min

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AU - Won, Moo Ho

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AU - Kim, Young Myeong

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