Endosomal and lysosomal effects of desferrioxamine: protection of HeLa cells from hydrogen peroxide-induced DNA damage and induction of cell-cycle arrest
Φόρτωση...
Ημερομηνία
Συγγραφείς
Doulias, P. T.
Christoforidis, S.
Brunk, U. T.
Galaris, D.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Free Radic Biol Med
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The role of endosomal/lysosomal redox-active iron in H2O2-induced nuclear DNA damage as well as in cell proliferation was examined using the iron chelator desferrioxamine (DFO). Transient transfections of HeLa cells with vectors encoding dominant proteins involved in the regulation of various routes of endocytosis (dynamin and Rab5) were used to show that DFO (a potent and rather specific iron chelator) enters cells by fluid-phase endocytosis and exerts its effects by chelating redox-active iron present in the endosomal/lysosomal compartment. Endocytosed DFO effectively protected cells against H2O2-induced DNA damage, indicating the importance of endosomal/lysosomal redox-active iron in these processes. Moreover, exposure of cells to DFO in a range of concentrations (0.1 to 100 microM) inhibited cell proliferation in a fluid-phase endocytosis-dependent manner. Flow cytometric analysis of cells exposed to 100 microM DFO for 24 h showed that the cell cycle was transiently interrupted at the G2/M phase, while treatment for 48 h led to permanent cell arrest. Collectively, the above results clearly indicate that DFO has to be endocytosed by the fluid-phase pathway to protect cells against H2O2-induced DNA damage. Moreover, chelation of iron in the endosomal/lysosomal cell compartment leads to cell cycle interruption, indicating that all cellular labile iron is propagated through this compartment before its anabolic use is possible.
Περιγραφή
Λέξεις-κλειδιά
Cell Cycle/*drug effects/physiology, Cell Division/drug effects, DNA Damage/*drug effects/physiology, Deferoxamine/*pharmacology, Dynamins/genetics/metabolism, Endosomes/*drug effects, HeLa Cells, Humans, Hydrogen Peroxide/*adverse effects, Iron/deficiency/metabolism, Iron Chelating Agents/pharmacology, Lysosomes/*drug effects, Mutation, Time Factors, rab5 GTP-Binding Proteins/genetics/metabolism
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/14583336
http://ac.els-cdn.com/S0891584903003964/1-s2.0-S0891584903003964-main.pdf?_tid=0079fefc3b6783a17cc9b49d5477f54a&acdnat=1332404444_2ad47ea03e6d8be3b22f992777121ef5
http://ac.els-cdn.com/S0891584903003964/1-s2.0-S0891584903003964-main.pdf?_tid=0079fefc3b6783a17cc9b49d5477f54a&acdnat=1332404444_2ad47ea03e6d8be3b22f992777121ef5
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής