Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Increased DNA double-strand breaks and enhanced apoptosis in patients with lupus nephritis
Δημιουργός/Συγγραφέας:	[EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L. Sfikakis P.P.
Εκδότης:	SAGE Publications Ltd
Ημερομηνία:	2015
Γλώσσα:	Αγγλικά
ISSN:	0961-2033
DOI:	10.1177/0961203314565413
Άλλο:	PubMed ID: 25542905
Περίληψη:	DNA double-strand breaks (DSBs) lead to mutations, genomic instability and apoptotic death, whereas accumulation of apoptotic cells results in excessive autoantigen presentation and autoantibody formation. We aimed to measure DSB levels in lupus nephritis, a severe complication of the prototypic systemic autoimmune disease. Methods: The intrinsic DNA damage and the apoptosis induction/DSB levels were evaluated in peripheral blood mononuclear cells of six patients and 10 healthy controls following exposure to genotoxic agents (melphalan, cisplatin) ex vivo. DSBs were assessed using immunofluorescence quantification of gH2AX foci and comet assay. Results: Intrinsic DNA damage was increased in lupus versus control cells in both assays (Olive Tail Moment units of 15.8±2.3 versus 3.0±1.4 in comet, p<0.01; % gH2AX-positive cells: 13.6±1.8 versus 4.6±0.9, p<0.01, respectively). Melphalan or cisplatin doses as low as 9.9±4.8 or 29.8±8.3 mg/ml, respectively, were sufficient to induce apoptosis in lupus cells; control cells required doses of 32.3±7.7 and 67.7±5.5 mg/ml, respectively. Drug-induced DSB levels were increased in lupus versus control cells, with the area under the curve (AUC) for melphalan-induced DSBs being 3050±610 (% γH2AX-positive staining cells)×(drug dose) in patients and 1580±350 in controls (p<0.05); the corresponding values for cisplatin-induced AUC were 13900±1800 for lupus and 4500±750 for controls (p<0.01). Interestingly, within either lupus patients or controls examined, the accumulation of DSBs correlated with apoptosis degrees (all p<0.01). Results in lupus cells were not associated with individual disease activity level or treatment modalities at the time of the study. Conclusion: These findings suggest a novel mechanism by which increased accumulation of DSBs may render cells more sensitive to apoptosis, thus contributing to the induction of systemic autoimmunity.
Τίτλος πηγής δημοσίευσης:	Lupus
Τόμος/Κεφάλαιο:	24
Τεύχος:	8
Σελίδες:	804-815
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	apoptosis DNA double-strand breaks intrinsic DNA damage Lupus nephritis
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2015 The Author(s).
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο