| Cell sensitivity to oxidative stress is influenced by ferritin autophagy. | |
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MedLine Citation:
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PMID: 21419217 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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To test the consequences of lysosomal degradation of differently iron-loaded ferritin molecules and to mimic ferritin autophagy under iron-overload and normal conditions, J774 cells were allowed to endocytose heavily iron-loaded ferritin, probably with some adventitious iron, (Fe-Ft) or iron-free apo-ferritin (apo-Ft). When cells subsequently were exposed to a bolus dose of hydrogen peroxide, apo-Ft prevented lysosomal membrane permeabilization (LMP), while Fe-Ft enhanced LMP. A 4h pulse of Fe-Ft initially increased oxidative stress-mediated LMP that was reversed after another 3h at standard culture conditions, suggesting that lysosomal iron is rapidly exported from lysosomes, with resulting upregulation of apo-ferritin that supposedly is autophagocytosed, thereby preventing LMP by binding intra-lysosomal redox-active iron. The obtained data suggest that upregulation of the stress-protein ferritin is a rapid adaptive mechanism that counteracts LMP and ensuing apoptosis during oxidative stress. In addition, prolonged iron starvation was found to induce apoptotic cell death that, interestingly, was preceded by LMP, suggesting that LMP is a more general phenomenon in apoptosis then so far recognized. The findings provide new insights into ageing and neurodegenerative diseases that are associated with enhanced amounts of cellular iron and show that lysosomal iron-loading sensitizes to oxidative stress. |
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Authors:
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Tino Kurz; Bertil Gustafsson; Ulf T Brunk |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-15 |
Journal Detail:
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Title: Free radical biology & medicine Volume: - ISSN: 1873-4596 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010. Published by Elsevier Inc. |
Affiliation:
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Division of Pharmacology, Faculty of Health Sciences, Linköping University, 581 85 Linköping, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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