Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner
Φόρτωση...
Ημερομηνία
Συγγραφείς
Barbouti, A.
Amorgianiotis, C.
Kolettas, E.
Kanavaros, P.
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
Apoptosis represents a physiological form of cell death, the perturbation of which may contribute to the development of several diseases connected with accumulation of unwanted cells or excessive cell loss. We have previously shown that the continuous presence of low concentrations of H2O2 (generated by the action of glucose oxidase) was able to inhibit caspase-mediated apoptosis in Jurkat cells. The main purpose of the present study was to elucidate the exact molecular mechanism(s) underlying this inhibitory action of H2O2. The results presented show that events like outer mitochondrial membrane permeabilization, release of cytochrome c from mitochondria, oligomerization of Apaf-1, and recruitment of procaspase-9 to apoptosomes were taking place normally, but further advancement toward activation of the execution caspases was interrupted when H2O2 was present during the apoptotic process. From the results presented in this work, it emerges that the inhibition of procaspase-9 autoactivation was probably due to the reversible oxidation of sensitive cysteine residues in this molecule. Remarkably, caspase-9 activation and the ensuing caspase cascade proceeded normally in the presence of H2O2 under conditions of iron deprivation, indicating that the inhibition of procaspase-9 activation was an iron-dependent process. Collectively, these results highlighted the potential role of available intracellular iron ions in signaling mechanisms related to apoptotic cell death.
Περιγραφή
Λέξεις-κλειδιά
Apoptosis/*drug effects, Apoptosomes/metabolism, Caspase 9/*antagonists & inhibitors/metabolism, Cysteine/metabolism, Cytochromes c/metabolism, Enzyme Activation/drug effects, Humans, Hydrogen Peroxide/*pharmacology, Iron/*metabolism, Jurkat Cells, Oxidation-Reduction
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/17936184
http://ac.els-cdn.com/S0891584907004480/1-s2.0-S0891584907004480-main.pdf?_tid=98d64aee6abe01e67c1c8bd509fd8e28&acdnat=1333090378_38433625bb9620c5db927dacb9b5e458
http://ac.els-cdn.com/S0891584907004480/1-s2.0-S0891584907004480-main.pdf?_tid=98d64aee6abe01e67c1c8bd509fd8e28&acdnat=1333090378_38433625bb9620c5db927dacb9b5e458
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