Cytoprotective effect of 1-nitro-2-phenylethane in mice pancreatic acinar cells subjected to taurocholate: Putative role of guanylyl cyclase-derived 8-nitro-cyclic-GMP
| Autor: | Saad Lahlou, Francisco J.B. Lima, Pedro Jorge Caldas Magalhães, F. Cosker |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Taurocholic Acid medicine.medical_specialty Vascular smooth muscle Apoptosis Acinar Cells Pharmacology medicine.disease_cause Biochemistry Nitric oxide Mice Necrosis chemistry.chemical_compound Internal medicine Benzene Derivatives medicine Animals Calcium Signaling Cyclic GMP Pancreas Cell damage Cells Cultured chemistry.chemical_classification Reactive oxygen species Chemistry medicine.disease Endocrinology Second messenger system Reactive Oxygen Species Soluble guanylyl cyclase Oxidative stress |
| Zdroj: | Biochemical Pharmacology. 91:191-201 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2014.07.030 |
| Popis: | The nitroderivative 1-nitro-2-phenylethane (NPE) was recently described as a compound possessing heme-dependent soluble guanylyl cyclase (sGC) stimulating properties in vascular smooth muscle cells. In this study, we tested such pharmacological property of NPE in mice pancreatic acinar cells subjected to the bile salt taurocholate, a type of pathological stimulus that simulates pancreatitis. Here, isolated acinar cells were treated with NPE in order to assess the role of sGC on the detrimental effects induced by taurocholate. NPE reduced taurocholate-elicited Ca2+ overload, production of reactive oxygen species (ROS), apoptosis, necrosis, and exerted a protective effect against mitochondrial membrane potential (ΔΨm) dissipation. These NPE-induced effects were abolished by pretreatment with ODQ and KT 5823, and after the blockade of nitric oxide (NO) synthase with l -NAME, inhibitors of key components of the sGC pathway. Contrarily to cGMP that alone increased ΔΨm collapse and cell damage, the cytoprotective effect of NPE on ΔΨm and cell necrosis was almost reproduced by 8-nitro-cGMP, a second messenger generated by sGC under oxidative stress conditions. In conclusion, putative sGC stimulation with NPE reveals its cytoprotective profile on pancreatic cells subjected to taurocholate. Moreover, ROS and NO conjunctly appear to drive sGC activity in pancreatic acinar cells to implement an adaptive mechanism in response to oxidative and Ca2+ stress through 8-nitro-cGMPsynthesis. |
| Databáze: | OpenAIRE |
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