ERK/Nrf2 pathway activation by caffeic acid in HepG2 cells alleviates its hepatocellular damage caused by t-butylhydroperoxide-induced oxidative stress

Sung Yong Yang, Min Cheol Pyo, Mi Hyun Nam, Kwang Won Lee

Research output: Contribution to journalArticle

Abstract

Background: Several studies have found that caffeic acid (CA), a well-known phytochemical, displays important antioxidant and anti-cancer activities. However, no evidence exists on the protective effect and its mechanisms that CA treatment alone has against oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells. Methods: Hepatoprotective activities such as cell viability, mRNA expression, and report gene assay were measured using HepG2 cell. Three types of genes and proteins related with detoxification in liver were used for measuring the hepatoprotective effects. Statistical analysis was performed using one-way ANOVA test and differences among groups were evaluated by Tukey's studentized range tests. Results: The present study indicate that treatment with CA up-regulates heme oxygenase-1 (HO-1) and glutamate-cysteine ligase (GCL) mRNA and protein expressions in a CA-dose-dependent manner. In addition, translocation of nuclear factor-E2 p45-related factor (Nrf2) from the cytoplasm to the nucleus and phosphorylation of extracellular signal-regulated kinase, ERK and c-Jun N-terminal kinase, JNK which have been shown to be involved in mitogen-activated protein kinases, MAPKs are significantly enhanced by CA treatment. Furthermore, in cell nuclei, CA enhances the 5′-flanking regulatory region of human antioxidant response element (ARE) and activates the ARE binding site. Conclusion: Therefore, CA proved to be a stimulant of the expression of detoxification enzymes such as HO-1, GCLC, and GCLM through the ERK/Nrf2 pathway, and it may be an effective chemoprotective agent for protecting liver damage against oxidative damage. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Article number139
JournalBMC Complementary and Alternative Medicine
Volume19
Issue number1
DOIs
Publication statusPublished - 2019 Jun 20

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tert-Butylhydroperoxide
MAP Kinase Signaling System
Hep G2 Cells
Oxidative Stress
Antioxidant Response Elements
Heme Oxygenase-1
Glutamate-Cysteine Ligase
Messenger RNA
JNK Mitogen-Activated Protein Kinases
5' Flanking Region
Nucleic Acid Regulatory Sequences
Liver
Extracellular Signal-Regulated MAP Kinases
Phytochemicals
caffeic acid
Mitogen-Activated Protein Kinases
Cell Nucleus
Cell Survival
Analysis of Variance
Cytoplasm

Keywords

  • Antioxidant response element
  • Caffeic acid
  • ERK/Nrf2 pathway
  • Glutamate-cysteine ligase
  • tert-butyl hydroperoxide

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

ERK/Nrf2 pathway activation by caffeic acid in HepG2 cells alleviates its hepatocellular damage caused by t-butylhydroperoxide-induced oxidative stress. / Yang, Sung Yong; Pyo, Min Cheol; Nam, Mi Hyun; Lee, Kwang Won.

In: BMC Complementary and Alternative Medicine, Vol. 19, No. 1, 139, 20.06.2019.

Research output: Contribution to journalArticle

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abstract = "Background: Several studies have found that caffeic acid (CA), a well-known phytochemical, displays important antioxidant and anti-cancer activities. However, no evidence exists on the protective effect and its mechanisms that CA treatment alone has against oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells. Methods: Hepatoprotective activities such as cell viability, mRNA expression, and report gene assay were measured using HepG2 cell. Three types of genes and proteins related with detoxification in liver were used for measuring the hepatoprotective effects. Statistical analysis was performed using one-way ANOVA test and differences among groups were evaluated by Tukey's studentized range tests. Results: The present study indicate that treatment with CA up-regulates heme oxygenase-1 (HO-1) and glutamate-cysteine ligase (GCL) mRNA and protein expressions in a CA-dose-dependent manner. In addition, translocation of nuclear factor-E2 p45-related factor (Nrf2) from the cytoplasm to the nucleus and phosphorylation of extracellular signal-regulated kinase, ERK and c-Jun N-terminal kinase, JNK which have been shown to be involved in mitogen-activated protein kinases, MAPKs are significantly enhanced by CA treatment. Furthermore, in cell nuclei, CA enhances the 5′-flanking regulatory region of human antioxidant response element (ARE) and activates the ARE binding site. Conclusion: Therefore, CA proved to be a stimulant of the expression of detoxification enzymes such as HO-1, GCLC, and GCLM through the ERK/Nrf2 pathway, and it may be an effective chemoprotective agent for protecting liver damage against oxidative damage. Graphical abstract: [Figure not available: see fulltext.]",
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T1 - ERK/Nrf2 pathway activation by caffeic acid in HepG2 cells alleviates its hepatocellular damage caused by t-butylhydroperoxide-induced oxidative stress

AU - Yang, Sung Yong

AU - Pyo, Min Cheol

AU - Nam, Mi Hyun

AU - Lee, Kwang Won

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N2 - Background: Several studies have found that caffeic acid (CA), a well-known phytochemical, displays important antioxidant and anti-cancer activities. However, no evidence exists on the protective effect and its mechanisms that CA treatment alone has against oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells. Methods: Hepatoprotective activities such as cell viability, mRNA expression, and report gene assay were measured using HepG2 cell. Three types of genes and proteins related with detoxification in liver were used for measuring the hepatoprotective effects. Statistical analysis was performed using one-way ANOVA test and differences among groups were evaluated by Tukey's studentized range tests. Results: The present study indicate that treatment with CA up-regulates heme oxygenase-1 (HO-1) and glutamate-cysteine ligase (GCL) mRNA and protein expressions in a CA-dose-dependent manner. In addition, translocation of nuclear factor-E2 p45-related factor (Nrf2) from the cytoplasm to the nucleus and phosphorylation of extracellular signal-regulated kinase, ERK and c-Jun N-terminal kinase, JNK which have been shown to be involved in mitogen-activated protein kinases, MAPKs are significantly enhanced by CA treatment. Furthermore, in cell nuclei, CA enhances the 5′-flanking regulatory region of human antioxidant response element (ARE) and activates the ARE binding site. Conclusion: Therefore, CA proved to be a stimulant of the expression of detoxification enzymes such as HO-1, GCLC, and GCLM through the ERK/Nrf2 pathway, and it may be an effective chemoprotective agent for protecting liver damage against oxidative damage. Graphical abstract: [Figure not available: see fulltext.]

AB - Background: Several studies have found that caffeic acid (CA), a well-known phytochemical, displays important antioxidant and anti-cancer activities. However, no evidence exists on the protective effect and its mechanisms that CA treatment alone has against oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells. Methods: Hepatoprotective activities such as cell viability, mRNA expression, and report gene assay were measured using HepG2 cell. Three types of genes and proteins related with detoxification in liver were used for measuring the hepatoprotective effects. Statistical analysis was performed using one-way ANOVA test and differences among groups were evaluated by Tukey's studentized range tests. Results: The present study indicate that treatment with CA up-regulates heme oxygenase-1 (HO-1) and glutamate-cysteine ligase (GCL) mRNA and protein expressions in a CA-dose-dependent manner. In addition, translocation of nuclear factor-E2 p45-related factor (Nrf2) from the cytoplasm to the nucleus and phosphorylation of extracellular signal-regulated kinase, ERK and c-Jun N-terminal kinase, JNK which have been shown to be involved in mitogen-activated protein kinases, MAPKs are significantly enhanced by CA treatment. Furthermore, in cell nuclei, CA enhances the 5′-flanking regulatory region of human antioxidant response element (ARE) and activates the ARE binding site. Conclusion: Therefore, CA proved to be a stimulant of the expression of detoxification enzymes such as HO-1, GCLC, and GCLM through the ERK/Nrf2 pathway, and it may be an effective chemoprotective agent for protecting liver damage against oxidative damage. Graphical abstract: [Figure not available: see fulltext.]

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