Heme Oxygenase-1, a Key Enzyme for the Cytoprotective Actions of Halophenols by Upregulating Nrf2 Expression via Activating Erk1/2 and PI3K/Akt in EA.hy926 Cells
| Autor: | Rui Ge, Xiu E. Feng, Jie Gao, De Peng Kong, Tai Gang Liang, Qing Shan Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Aging Article Subject Cell Survival NF-E2-Related Factor 2 p38 mitogen-activated protein kinases Blotting Western Apoptosis Biochemistry Cell Line Wortmannin Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Phenols Downregulation and upregulation Humans Phosphorylation lcsh:QH573-671 Heme Protein kinase B PI3K/AKT/mTOR pathway Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Tumor Necrosis Factor-alpha lcsh:Cytology Hydrogen Peroxide Cell Biology General Medicine Flow Cytometry Cell biology Heme oxygenase Oxidative Stress 030104 developmental biology chemistry 030220 oncology & carcinogenesis Proto-Oncogene Proteins c-akt Heme Oxygenase-1 Research Article Signal Transduction |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2017 (2017) Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0994 1942-0900 |
| Popis: | Increasing evidence has demonstrated that heme oxygenase-1 (HO-1) is a key enzyme triggered by cellular stress, exhibiting cytoprotective, antioxidant, and anti-inflammatory abilities. Previously, we prepared a series of novel active halophenols possessing strong antioxidant activities in vitro and in vivo. In the present study, we demonstrated that these halophenols exhibited significant protective effects against H2O2-induced injury in EA.hy926 cells by inhibition of apoptosis and ROS and TNF-αproduction, as well as induction of the upregulation of HO-1, the magnitude of which correlated with their cytoprotective actions. Further experiments which aimed to determine the mechanistic basis of these actions indicated that the halophenols induced the activation of Nrf2, Erk1/2, and PI3K/Akt without obvious effects on the phosphorylation of p38, JNK, or the expression of PKC-δ. This was validated with the use of PD98059 and Wortmannin, specific inhibitors of Erk1/2 and PI3K, respectively. Overall, our study is the first to demonstrate that the cytoprotective actions of halophenols involve their antiapoptotic, antioxidant, and anti-inflammatory abilities, which are mediated by the upregulation of Nrf2-dependent HO-1 expression and reductions in ROS and TNF-αgeneration via the activation of Erk1/2 and PI3K/Akt in EA.hy926 cells. HO-1 may thus be an important potential target for further research into the cytoprotective actions of halophenols. |
| Databáze: | OpenAIRE |
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