Naturally-derived diterpenoid sphaeropsidin C as an activator of Nrf2/ARE pathway and its potential capability of relieving intracellular oxidative stress in human lung epithelial cells - 30/11/19
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Graphical abstract |
Highlights |
• | SC is identified to be an activator of Nrf2/ARE signaling pathway. |
• | SC-induced Nrf2 activation is a process requiring protein kinases. |
• | SC protects human lung epithelial cells against oxidative insults. |
• | Isopimarane-type diterpenoid is a promising skeleton for developing Nrf2 activators. |
Abstract |
Oxidative stress is closely associated to the onset and progression of many human diseases. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway using naturally-derived molecules is an efficient strategy for alleviating the intracellular oxidative insults, and thus blocking the pathogenesis of oxidative stress-induced diseases. In the present study, a naturally-derived isopimarane-type diterpenoid sphaeropsidin C (SC) was identified to be an activator of Nrf2/ARE signaling pathway. Our data indicated that SC was able to stimulate Nrf2-mediated defensive system through promoting Nrf2 translocation, inhibiting Nrf2 ubiquitination, and enhancing Nrf2 stability in normal human lung epithelial Beas-2B cells. Furthermore, SC-induced Nrf2 activation required the involvement of protein kinases, exemplified by protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). It alleviated sodium arsenite [As(III)]-induced intracellular oxidative stress in an Nrf2-dependent manner. These results suggested that SC displayed potential application for the prevention and therapy against oxidative stress-induced diseases. Moreover, isopimarane-type diterpenoid represents a promising skeleton for developing Nrf2 activators.
Le texte complet de cet article est disponible en PDF.Abbreviations : AO, ARE, As(III), BSA, CHX, COPD, DAPI, γ-GCS, GST, HO-1, Keap1, MAPK, MTT, NQO1, Nrf2, PERK, PKC, PI3K, PPI, QR, RNS, ROS, SF, tBHQ
Keywords : Sphaeropsidin C, Diterpenoid, Nrf2, Oxidative stress
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Vol 121
Article 109669- janvier 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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