Ropivacaine regulates the expression and function of heme oxygenase-1 - 29/05/18
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Graphical abstract |
Highlights |
• | Ropivacaine increased HO-1 in SHSY5Y cells in a time- and dose-dependent manner. |
• | The effects of ropivacaine on HO-1 expression are mediated by p38 and Nrf2. |
• | Ropivacaine induced activation of the ARE-luciferase reporter. |
• | Inhibition of HO-1 exacerbated ropivacaine-induced oxidative stress and cell death. |
Abstract |
As a new generation of amide-type local anesthetics (LAs), ropivacaine has been widely used for pain management in clinical settings. Increasing evidence has shown that administration of ropivacaine causes cytotoxic effects and apoptosis. However, the underlying molecular mechanisms still need to be elucidated. In the current study, our results indicated that ropivacaine treatment caused a significant induction of heme oxygenase-1 (HO-1) at both the mRNA and protein levels in human SHSY5Y cells. Levels of HO-1 mRNA and protein peaked at 1 h and 18 h, respectively, in response to ropivacaine treatment. Additionally, ropivacaine treatment enhanced HO-1 activity in a dose-dependent manner. Interestingly, we found that ropivacaine treatment induced phosphorylation of p38. Blockage of p38 phosphorylation with its specific inhibitor SB203580 or by transfection with p38 siRNA restrained ropivacaine-stimulated HO-1 expression. Additionally, we found that ropivacaine treatment promoted nuclear translocation of Nrf2 and amplified ARE promoter activity. Silencing of Nrf2 abolished ropivacaine-induced HO-1 expression. Notably, we found that inhibition of HO-1 activity promoted ropivacaine-induced production of reactive oxygen species (ROS), deletion of reduced glutathione (GSH), and release of lactate dehydrogenase (LDH), suggesting that induction of HO-1 by ropivacaine acted as a compensatory survival response against ropivacaine.
Le texte complet de cet article est disponible en PDF.Keywords : Heme oxygenase-1, Local anesthetics, Ropivacaine, Nrf2, ROS
Plan
Vol 103
P. 284-289 - juillet 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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