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Punicalagin induces Nrf2 translocation and HO-1 expression via PI3K/Akt, protecting rat intestinal epithelial cells from oxidative stress
- Source :
- International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 32(5)
- Publication Year :
- 2016
-
Abstract
- Oxidative stress plays a central role in heat stress-induced gastrointestinal injury. Punicalagin (PUN), a major polyphenol abundant in pomegranate fruit, husk and juice, exhibits antioxidative effects. In this study we used a heat stress model to investigate the intestinal protection effect of PUN and the underlying mechanisms.IEC-6 cells were pretreated with PUN for 6 h and exposed to 42 °C for 6 h. Intracellular reactive oxygen species levels, malondialdehyde, nitrogen oxide, and superoxide dismutase activity were measured. IEC-6 cells were treated with PUN at different times and doses, the protein levels of haeme oxygenase-1 (HO-1) were evaluated. The nuclear translocation of the transcription factor NF-erythroid 2-related factor (Nrf2) and the phosphorylation level of PI3K/Akt were also investigated.PUN significantly decreased the heat stress-induced cell death and apoptosis. Heat stress increased reactive oxygen species, malondialdehyde and nitrogen oxide production, while it decreased superoxide dismutase activity. These effects were markedly inversed when the cells were pretreated with PUN. Furthermore, PUN treatment induced the expression of HO-1 and increased Nrf2 nuclear translocation in a time- and dose-dependent manner. The Nrf2-related cytoprotective effects of PUN were via the PI3K/Akt signalling pathway, as LY294002, a specific PI3K/Akt inhibitor, suppressed the PUN-induced nuclear translocation of Nrf2, the HO-1 up-regulation and the protective effect of PUN against oxidative stress.PUN protects IEC-6 cells against oxidative stress by up-regulating the expression of HO-1 via a mechanism that involves PI3K/Akt activation and Nrf2 translocation.
- Subjects :
- 0301 basic medicine
Cancer Research
Hot Temperature
Physiology
Cell Survival
NF-E2-Related Factor 2
medicine.disease_cause
Nitric Oxide
Antioxidants
Nitric oxide
Cell Line
Superoxide dismutase
03 medical and health sciences
chemistry.chemical_compound
Phosphatidylinositol 3-Kinases
Physiology (medical)
medicine
Animals
Protein kinase B
PI3K/AKT/mTOR pathway
Punicalagin
chemistry.chemical_classification
Reactive oxygen species
biology
Chemistry
Superoxide Dismutase
Epithelial Cells
Malondialdehyde
Hydrolyzable Tannins
Cell biology
Rats
Intestines
Oxidative Stress
030104 developmental biology
Biochemistry
Heme Oxygenase (Decyclizing)
biology.protein
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Oxidative stress
Subjects
Details
- ISSN :
- 14645157
- Volume :
- 32
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
- Accession number :
- edsair.doi.dedup.....51e2be407bd8d8ad82679eb737f79b83