Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress

Autor: Zongyao Zou, Hang Ma, Xiaoli Ye, Min Feng, Kai He, Yue Wang, Yinran Hu, Xuegang Li, Yubo Xiao
Rok vydání: 2017
Předmět:
0301 basic medicine
Embryo
Nonmammalian
Antioxidant
Berberine
medicine.medical_treatment
Amidines
Pharmacology
medicine.disease_cause
Antioxidants
Lipid peroxidation
chemistry.chemical_compound
0302 clinical medicine
Heart Rate
NAD(P)H Dehydrogenase (Quinone)
Phosphorylation
Zebrafish
chemistry.chemical_classification
biology
Glutathione peroxidase
Hep G2 Cells
General Medicine
Oxidants
Glutathione
Biochemistry
030220 oncology & carcinogenesis
Signal Transduction
Programmed cell death
NF-E2-Related Factor 2
Superoxide dismutase
03 medical and health sciences
medicine
Animals
Humans
Protein kinase B
Glutathione Peroxidase
Dose-Response Relationship
Drug
Superoxide Dismutase
JNK Mitogen-Activated Protein Kinases
Zebrafish Proteins
Enzyme Activation
Oxidative Stress
030104 developmental biology
chemistry
Hepatocytes
biology.protein
Lipid Peroxidation
Proto-Oncogene Proteins c-akt
Oxidative stress
Zdroj: Biomedicine & Pharmacotherapy. 85:313-322
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2016.11.031
Popis: Coptisine (COP) is one of the main active constituents of Coptidis Rhizoma. Previous studies have clarified that COP possesses antioxidant activity, but its defensive effects against pathological characteristics accompanied by oxidative damage in animal models and antioxidant mechanism are still unclear. Therefore, our purpose was to confirm the antioxidant activity of COP and explore its mechanism of action. We first detected the effects of COP on intracellular reactive oxygen species (ROS), heart beating rate, lipid peroxidation and cell death in zebrafish model with AAPH-induced oxidative stress. The results showed that COP of 10μg/mL significantly reduced ROS production, the increase of heart beating rate, lipid peroxidation and cell death by 41.3%, 24.5%, 26.5% and 30.0%, respectively. In addition, COP of 0.8μg/mL also decreased ROS, increased glutathione (GSH) content and elevated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 40.1%, 19.8%, 18.3% and 49.3%, respectively in HepG2 cells. Further assays were carried out to explore the mRNA expression in zebrafish and protein expression of key factors in HepG2 cells. We demonstrated that COP up-regulated phase II antioxidant enzymes NAD(P)H/quinone oxidoreductase 1 (NQO1) through activating the nuclear factor erythroid-2 related factor 2 (Nrf2). Moreover, as the upstream signalings of Nrf2, the protein kinase B (Akt) and c-Jun NH2-terminal kinase (JNK) signalings were also induced by COP. And up-regulating Nrf2-mediated NQO1 expression of COP was in Akt and JNK-dependent manner. Taken together, COP exerted its antioxidant activity against AAPH-induced toxicity involving in activating Akt and JNK/Nrf2/NQO1 pathway.
Databáze: OpenAIRE
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