Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells

Background: The beneficial effects of compound K (CK) on different chronic diseases have been shown to be at least related to antioxidant action. Nevertheless, since its antioxidant activity in human retinal pigment epithelial (RPE) cells is still unknown, here we investigated whether CK alleviates...

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Main Authors: Cheol Park, Hee-Jae Cha, Kyoung-Seob Song, Heui-Soo Kim, EunJin Bang, Hyesook Lee, Cheng-Yun Jin, Gi-Young Kim, Yung Hyun Choi
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Journal of Ginseng Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1226845322001233
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author Cheol Park
Hee-Jae Cha
Kyoung-Seob Song
Heui-Soo Kim
EunJin Bang
Hyesook Lee
Cheng-Yun Jin
Gi-Young Kim
Yung Hyun Choi
author_facet Cheol Park
Hee-Jae Cha
Kyoung-Seob Song
Heui-Soo Kim
EunJin Bang
Hyesook Lee
Cheng-Yun Jin
Gi-Young Kim
Yung Hyun Choi
author_sort Cheol Park
collection DOAJ
description Background: The beneficial effects of compound K (CK) on different chronic diseases have been shown to be at least related to antioxidant action. Nevertheless, since its antioxidant activity in human retinal pigment epithelial (RPE) cells is still unknown, here we investigated whether CK alleviates oxidative stress-stimulated damage in RPE ARPE-19 cells. Methods: The cytoprotective consequence of CK in hydrogen peroxide (H2O2)-treated cells was evaluated by cell viability, DNA damage, and apoptosis assays. Fluorescence analysis and immunoblotting were performed to investigate the inhibitory action of CK on reactive oxygen species (ROS) production and mitochondrial dysfunction. Results: H2O2-promoted cytotoxicity, oxidative stress, DNA damage, mitochondrial impairment, and apoptosis were significantly attenuated by CK in ARPE-19 cells. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation level and its shuttling to the nucleus were increased, which was correlated with upregulated activation of heme oxygenase-1 (HO-1). However, zinc protoporphyrin, a blocker of HO-1, significantly abrogated the preventive action of CK in H2O2-treated ARPE-19 cells. Conclusion: This study indicates that activation of Nrf2/HO-1 signaling by CK plays an important role in rescuing ARPE-19 cells from oxidative cellular damage.
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spelling doaj.art-b1bcbe2766f5403183aa6aca9e5a0e6a2023-03-01T04:31:13ZengElsevierJournal of Ginseng Research1226-84532023-03-01472311318Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cellsCheol Park0Hee-Jae Cha1Kyoung-Seob Song2Heui-Soo Kim3EunJin Bang4Hyesook Lee5Cheng-Yun Jin6Gi-Young Kim7Yung Hyun Choi8Division of Basic Sciences, Dong-eui University, Busan, Republic of KoreaCollege of Medicine, Kosin University, Busan, Republic of KoreaCollege of Medicine, Kosin University, Busan, Republic of KoreaDepartment of Biological Sciences, Pusan National University, Busan, Republic of KoreaAnti-Aging Research Center and Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, Republic of KoreaDepartment of Convergence Medicine, Pusan National University, Yangsan, Republic of KoreaCollege of Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Marine Life Science, Jeju National University, Jeju, Republic of KoreaAnti-Aging Research Center and Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, Republic of Korea; Corresponding author. Department of Biochemistry, Dong-eui University College of Korean Medicine, 52-57, Yangjeong-ro, Busanjin-gu Busan, 47227, Republic of Korea.Background: The beneficial effects of compound K (CK) on different chronic diseases have been shown to be at least related to antioxidant action. Nevertheless, since its antioxidant activity in human retinal pigment epithelial (RPE) cells is still unknown, here we investigated whether CK alleviates oxidative stress-stimulated damage in RPE ARPE-19 cells. Methods: The cytoprotective consequence of CK in hydrogen peroxide (H2O2)-treated cells was evaluated by cell viability, DNA damage, and apoptosis assays. Fluorescence analysis and immunoblotting were performed to investigate the inhibitory action of CK on reactive oxygen species (ROS) production and mitochondrial dysfunction. Results: H2O2-promoted cytotoxicity, oxidative stress, DNA damage, mitochondrial impairment, and apoptosis were significantly attenuated by CK in ARPE-19 cells. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation level and its shuttling to the nucleus were increased, which was correlated with upregulated activation of heme oxygenase-1 (HO-1). However, zinc protoporphyrin, a blocker of HO-1, significantly abrogated the preventive action of CK in H2O2-treated ARPE-19 cells. Conclusion: This study indicates that activation of Nrf2/HO-1 signaling by CK plays an important role in rescuing ARPE-19 cells from oxidative cellular damage.http://www.sciencedirect.com/science/article/pii/S1226845322001233ApoptosisARPE-19 cellsCompound KNrf2/HO-1Oxidative stress
spellingShingle Cheol Park
Hee-Jae Cha
Kyoung-Seob Song
Heui-Soo Kim
EunJin Bang
Hyesook Lee
Cheng-Yun Jin
Gi-Young Kim
Yung Hyun Choi
Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells
Journal of Ginseng Research
Apoptosis
ARPE-19 cells
Compound K
Nrf2/HO-1
Oxidative stress
title Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells
title_full Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells
title_fullStr Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells
title_full_unstemmed Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells
title_short Nrf2-mediated activation of HO-1 is required in the blocking effect of compound K, a ginseng saponin metabolite, against oxidative stress damage in ARPE-19 human retinal pigment epithelial cells
title_sort nrf2 mediated activation of ho 1 is required in the blocking effect of compound k a ginseng saponin metabolite against oxidative stress damage in arpe 19 human retinal pigment epithelial cells
topic Apoptosis
ARPE-19 cells
Compound K
Nrf2/HO-1
Oxidative stress
url http://www.sciencedirect.com/science/article/pii/S1226845322001233
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