دورية أكاديمية
Melatonin induces the expression of Nrf2-regulated antioxidant enzymes via PKC and Ca2+ influx activation in mouse pancreatic acinar cells
| العنوان: | Melatonin induces the expression of Nrf2-regulated antioxidant enzymes via PKC and Ca2+ influx activation in mouse pancreatic acinar cells |
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| المؤلفون: | Santofimia-Castaño, Patricia, Clea Ruy, Deborah, Garcia-Sanchez, Lourdes, Jimenez-Blasco, Daniel, Fernandez-Bermejo, Miguel, Bolaños, Juan P., Salido, Gines M., Gonzalez, Antonio |
| المساهمون: | National Institutes of Health (US), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación Tatiana Pérez de Guzmán el Bueno, European Commission, Junta de Extremadura |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2015 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Calcium, Antioxidant responses, Protein kinase C, Nrf2, Melatonin, Pancreas |
| الوصف: | The goal of this study was to evaluate the potential activation of the nuclear factor erythroid 2-related factor and the antioxidant-responsive element (Nrf2–ARE) signaling pathway in response to melatonin in isolated mouse pancreatic acinar cells. Changes in intracellular free Ca2+ concentration were followed by fluorimetric analysis of fura-2-loaded cells. The activations of PKC and JNK were measured by Western blot analysis. Quantitative reverse transcription–polymerase chain reaction was employed to detect the expression of Nrf2-regulated antioxidant enzymes. Immunocytochemistry was employed to determine nuclear location of phosphorylated Nrf2, and the cellular redox state was monitored following MitoSOX Red-derived fluorescence. Our results show that stimulation of fura-2-loaded cells with melatonin (1 µM to 1 mM), in the presence of Ca2+ in the extracellular medium, induced a slow and progressive increase of [Ca2+]c toward a stable level. Melatonin did not inhibit the typical Ca2+ response induced by CCK-8 (1 nM). When the cells were challenged with indoleamine in the absence of Ca2+ in the extracellular solution (medium containing 0.5 mM EGTA) or in the presence of 1 mM LaCl3, to inhibit Ca2+ entry, we could not detect any change in [Ca2+]c. Nevertheless, CCK-8 (1 nM) was able to induce the typical mobilization of Ca2+. When the cells were incubated with the PKC activator PMA (1 µM) in the presence of Ca2+ in the extracellular medium, we observed a response similar to that noted when the cells were challenged with melatonin 100 µM. However, in the presence of Ro31-8220 (3 µM), a PKC inhibitor, stimulation of cells with melatonin failed to evoke changes in [Ca2+]c. Immunoblots, using an antibody specific for phospho-PKC, revealed that melatonin induces PKCα activation, either in the presence or in the absence of external Ca2+. Melatonin induced the phosphorylation and nuclear translocation of the transcription factor Nrf2, and evoked a concentration-dependent increase in the expression of the antioxidant ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0891-5849 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/EC/FP7/608381; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-41177-R; Postprint; https://doi.org/10.1016/j.freeradbiomed.2015.06.033Test; Sí; e-issn: 1873-4596; Free Radical Biology and Medicine 87: 226-236 (2015); http://hdl.handle.net/10261/156873Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100003329Test; http://dx.doi.org/10.13039/501100004587Test; http://dx.doi.org/10.13039/100000002Test; http://dx.doi.org/10.13039/501100010805Test; http://dx.doi.org/10.13039/501100014181Test |
| DOI: | 10.1016/j.freeradbiomed.2015.06.033 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100003329 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/100000002 |
| DOI: | 10.13039/501100010805 |
| DOI: | 10.13039/501100014181 |
| الإتاحة: | https://doi.org/10.1016/j.freeradbiomed.2015.06.033Test https://doi.org/10.13039/501100000780Test https://doi.org/10.13039/501100003329Test https://doi.org/10.13039/501100004587Test https://doi.org/10.13039/100000002Test https://doi.org/10.13039/501100010805Test https://doi.org/10.13039/501100014181Test http://hdl.handle.net/10261/156873Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.2DF42912 |
| قاعدة البيانات: | BASE |
| تدمد: | 08915849 |
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| DOI: | 10.1016/j.freeradbiomed.2015.06.033 |