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Titolo:
Cladribine induces apoptosis in human leukaemia cells by caspase-dependentand -independent pathways acting on mitochondria
Autore:
Marzo, I; Perez-Galan, P; Giraldo, P; Rubio-Felix, D; Anel, A; Naval, J;
Indirizzi:
Univ Zaragoza, Fac Ciencias, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain Univ Zaragoza Zaragoza Spain E-50009 & Celular, E-50009 Zaragoza, Spain Hosp Univ Miguel Servet, Hematol Serv, Zaragoza, Spain Hosp Univ Miguel Servet Zaragoza Spain t, Hematol Serv, Zaragoza, Spain
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 359, anno: 2001,
parte:, 3
pagine: 537 - 546
SICI:
0264-6021(20011101)359:<537:CIAIHL>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC LYMPHOCYTIC-LEUKEMIA; CYTOCHROME-C RELEASE; IN-VITRO; PURINE ANALOGS; THYMOCYTE APOPTOSIS; NUCLEAR APOPTOSIS; FLOW-CYTOMETRY; FAS/FAS-LIGAND; DEATH; DNA;
Keywords:
AIF; apoptosis-inducing factor; 2-chloro-2 '-deoxyadenosine; Mcl-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Naval, J Univ Zaragoza, Fac Ciencias, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain Univ Zaragoza Zaragoza Spain E-50009 r, E-50009 Zaragoza, Spain
Citazione:
I. Marzo et al., "Cladribine induces apoptosis in human leukaemia cells by caspase-dependentand -independent pathways acting on mitochondria", BIOCHEM J, 359, 2001, pp. 537-546

Abstract

We have studied the role of caspases and mitochondria in apoptosis inducedby 2-chloro-2'-deoxyadenosine (cladribine) in several human leukaemic celllines. Cladribine treatment induced mitochondrial transmembrane potential (AT.) loss, phosphatidylserine exposure, caspase activation and developmentof typical apoptotic morphology in JM1 (pre-B), Jurkat (T) and U937 (promonocytic) cells. Western-blot analysis of cell extracts revealed the activation of at least caspases 3, 6, 8 and 9. Co-treatment with Z-VAD-fmk (benzyloxy-carbonyl-Val-Ala-Asp-fluoromethylketone), a general caspase inhibitor, significantly prevented cladribine-induced death in JM1 and Jurkat cells for the first approximate to 40 h, but not for longer times. Z-VAD-fmk also partly prevented some morphological and biochemical features of apoptosis inU937 cells, but not cell death. Coincubation with selective caspase inhibitors Ac-DEVD-CHO (N-acetyl-Asp-Glu-Val-Asp-aldehyde), Ac-LEHD-CHO (N-acetyl-Leu-Glu-His-Asp-aldehyde) or Z-IETD-fmk (benzyloxy-carbonyl-Ile-Glu-Thr-Asp-fluoromethylketone), inhibition of protein synthesis with cycloheximide or cell-cycle arrest with aphidicolin did not prevent cell death. Overexpression of Bcl-2, but not CrmA, efficiently prevented death in Jurkat cells. In all cell lines, death was always preceded by AT. loss and accompanied by the translocation of the protein apoptosis-inducing factor (AIF) from mitochondria to the nucleus. These results suggest that caspases are differentially involved in induction and execution of apoptosis depending on the leukaemic cell lineage. In any case, Delta Psi (m) loss marked the point of no return in apoptosis and may be caused by two different pathways, one caspase-dependent and the other caspase-independent. Execution of apoptosis was always performed after Delta Psi (m) loss by a caspase-9-triggered caspase cascade and the action of AIF.

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Documento generato il 19/09/20 alle ore 21:57:25