Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus
Δημιουργός/Συγγραφέας:	[EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L. Vougas K. Gorgoulis V.G. Sfikakis P.P.
Εκδότης:	BioMed Central Ltd.
Ημερομηνία:	2016
Γλώσσα:	Αγγλικά
ISSN:	1478-6354
DOI:	10.1186/s13075-016-1081-3
Άλλο:	PubMed ID: 27492607
Περίληψη:	Background: Excessive autoantibody production characterizing systemic lupus erythematosus (SLE) occurs irrespective of the disease's clinical status and is linked to increased lymphocyte apoptosis. Herein, we tested the hypothesis that defective DNA damage repair contributes to increased apoptosis in SLE. Methods: We evaluated nucleotide excision repair at the N-ras locus, DNA double-strand breaks repair and apoptosis rates in peripheral blood mononuclear cells from anti-dsDNA autoantibody-positive patients (six with quiescent disease and six with proliferative nephritis) and matched healthy controls following ex vivo treatment with melphalan. Chromatin organization and expression levels of DNA repair- and apoptosis-associated genes were also studied in quiescent SLE. Results: Defective nucleotide excision repair and DNA double-strand breaks repair were found in SLE, with lupus nephritis patients showing higher DNA damage levels than those with quiescent disease. Melphalan-induced apoptosis rates were higher in SLE than control cells and correlated inversely with DNA repair efficiency. Chromatin at the N-ras locus was more condensed in SLE than controls, while treatment with the histone deacetylase inhibitor vorinostat resulted in hyperacetylation of histone H4, chromatin decondensation, amelioration of DNA repair efficiency and decreased apoptosis. Accordingly, genes involved in DNA damage repair and signaling pathways, such as DDB1, ERCC2, XPA, XPC, MRE11A, RAD50, PARP1, MLH1, MLH3, and ATM were significantly underexpressed in SLE versus controls, whereas PPP1R15A, BARD1 and BBC3 genes implicated in apoptosis were significantly overexpressed. Conclusions: Epigenetically regulated functional abnormalities of DNA repair machinery occur in SLE, regardless of clinical disease activity, and may promote lymphocyte apoptosis. Approaches to correct these abnormalities may be of therapeutic value in SLE.
Τίτλος πηγής δημοσίευσης:	Arthritis Research and Therapy
Τόμος/Κεφάλαιο:	18
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Ανοσολογία[EN] Immunology
Λέξεις-Κλειδιά:	Apoptosis Chromatin organization DNA double-strand breaks repair Histone deacetylase inhibitor Nucleotide excision repair Systemic lupus erythematosus
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2016 The Author(s).
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Σημειώσεις:	The study was funded by the Special Account for Research Grants of the National and Kapodistrian University of Athens, Athens, Greece (ELKE Grant number 974).
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο