| ER signaling regulation drives the switch between autophagy and apoptosis in NRK-52E cells exposed to cisplatin. | |
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MedLine Citation:
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PMID: 22146761 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Cisplatin (cisPt) use in chemotherapy is limited by the occurrence of a severe nephrotoxicity. Both autophagy and apoptosis seem to contribute in kidney response to cisPt, however their cross-talk is still controversial, since the role played by autophagy (cytoprotective or harmful) and the cellular site driving their switch, are still unclear. Here, we used a multidisciplinary approach to study the correlation between autophagy and apoptosis in renal NRK-52E cells exposed to cisPt. We show two "sensitivity-thresholds" to cisPt, stating whether apoptosis or autophagy would develop: 10μM dose of cisPt activated autophagy that preserved cell homeostasis; however 3-methyladenine co-administration affected cell viability and induced apoptosis. In contrast, 50μM cisPt determined cell death by apoptosis, whereas the pre-conditioning with taurine contributed to cell rescue, delaying apoptosis and maintaining autophagy. Hence, autophagy protects NRK-52E cells from cisPt injury. By studying the expression of ER specific hallmarks, such as GRP78, GRP94 and GADD153/CHOP, we found a possible pivotal role of ER signaling modulation in the crosstalk between autophagy and apoptosis induced by cisPt. To the best of our knowledge, this is the first demonstration that taurine enhances autophagic protection against apoptosis by reducing ER stress, thus making it possible to develop new strategies to reduce severe cisPt-induced side-effects such as nephrotoxicity. |
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Authors:
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Francesca Rovetta; Alessandra Stacchiotti; Antonella Consiglio; Moris Cadei; Pier Giovanni Grigolato; Antonio Lavazza; Rita Rezzani; Maria Francesca Aleo |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-28 |
Journal Detail:
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Title: Experimental cell research Volume: - ISSN: 1090-2422 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
Affiliation:
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Unit of Biochemistry, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, viale Europa 11, 25123 Brescia, Italy; Interuniversity Institute of Miology (IIM), Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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