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

Autor: Mi Hyun Nam, Sung Yong Yang, Min Cheol Pyo, Kwang Won Lee
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Chemoprotective agent
MAPK/ERK pathway
Cell Survival
NF-E2-Related Factor 2
Glutamate-Cysteine Ligase
medicine.disease_cause
Protective Agents
03 medical and health sciences
0302 clinical medicine
Caffeic Acids
tert-Butylhydroperoxide
Antioxidant response element
medicine
Humans
Viability assay
Extracellular Signal-Regulated MAP Kinases
Caffeic acid
Kinase
GCLM
Chemistry
tert-butyl hydroperoxide
Liver Neoplasms
JNK Mitogen-Activated Protein Kinases
lcsh:Other systems of medicine
General Medicine
Hep G2 Cells
lcsh:RZ201-999
Antioxidant Response Elements
030205 complementary & alternative medicine
Cell biology
Oxidative Stress
GCLC
Complementary and alternative medicine
Liver
030220 oncology & carcinogenesis
Phosphorylation
Reactive Oxygen Species
ERK/Nrf2 pathway
Oxidative stress
Heme Oxygenase-1
Research Article
Zdroj: BMC Complementary and Alternative Medicine
BMC Complementary and Alternative Medicine, Vol 19, Iss 1, Pp 1-13 (2019)
ISSN: 1472-6882
Popis: 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 Electronic supplementary material The online version of this article (10.1186/s12906-019-2551-3) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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