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Caspase-activated DNase is necessary and sufficient for oligonucleosomal DNA breakdown, but not for chromatin disassembly during caspase-dependent apoptosis of LN-18 glioblastoma cells
Sánchez-Osuna, María (Universitat Autònoma de Barcelona. Institut de Neurociències)
Garcia i Belinchón, Maria Mercè (Universitat Autònoma de Barcelona. Institut de Neurociències)
Iglesias Guimarais, Victoria (Universitat Autònoma de Barcelona. Institut de Neurociències)
Gil Guiñon, Estel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Casanelles Abella, Elisenda (Universitat Autònoma de Barcelona. Institut de Neurociències)
Yuste Mateos, Víctor J. (Víctor José) (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data: 2014
Resum: Caspase-dependent apoptosis is a controlled type of cell death characterized by oligonucleosomal DNA breakdown and major nuclear morphological alterations. Other kinds of cell death do not share these highly distinctive traits because caspase-activated DNase (DFF40/CAD) remains inactive. Here, we report that human glioblastoma multiforme-derived LN-18 cells do not hydrolyze DNA into oligonucleosomal fragments after apoptotic insult. Furthermore, their chromatin remains packaged into a single mass, with no signs of nuclear fragmentation. However, ultrastructural analysis reveals that nuclear disassembly occurs, although compacted chromatin does not localize into apoptotic nuclear bodies. Caspases become properly activated, and ICAD, the inhibitor of DFF40/CAD, is correctly processed. Using cell-free in vitro assays, we show that chromatin from isolated nuclei of LN-18 cells is suitable for hydrolysis into oligonuclesomal fragments by staurosporine-pretreated SH-SY5Y cytoplasms. However, staurosporine-pretreated LN-18 cytoplasms do not induce DNA laddering in isolated nuclei from either LN-18 or SH-SY5Y cells because LN-18 cells express lower amounts of DFF40/CAD. DFF40/CAD overexpression makes LN-18 cells fully competent to degrade their DNA into oligonucleosome-sized fragments, and yet they remain unable to arrange their chromatin into nuclear clumps after apoptotic insult. Indeed, isolated nuclei from LN-18 cells were resistant to undergoing apoptotic nuclear morphology in vitro. The use of LN-18 cells has uncovered a previously unsuspected cellular model, whereby a caspase-dependent chromatin package is DFF40/CAD-independent, and DFF40/CAD-mediated double-strand DNA fragmentation does not warrant the distribution of the chromatin into apoptotic nuclear bodies. The studies highlight a not-yet reported DFF40/CAD-independent mechanism driving conformational nuclear changes during caspase-dependent cell death.
Nota: Número d'acord de subvenció MINECO/SAF2012-31485
Nota: Número d'acord de subvenció AGAUR/SGR2009-346
Nota: Número d'acord de subvenció MICINN/BES-2099-028572
Nota: Número d'acord de subvenció MICINN/TRA2009-0185
Nota: Altres ajuts: FPU MICINN, MEC programa Ramón y Cajal
Drets: Tots els drets reservats
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: Apoptosis ; Apoptotic Nuclear Morphology ; Caspase ; Chromatin Disassembly ; DFF40/CAD ; DNA ; Deoxyribonuclease (DNase) ; Nucleus ; Oligonucleosomal DNA fragmentation
Publicat a: Journal of Biological Chemistry, Vol. 289 Núm. 27 (2014) , p. 18752-18760, ISSN 0021-9258

DOI: 10.1074/jbc.M114.550020

18 p, 9.5 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Neurociències (INc)
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 Registre creat el 2015-09-28, darrera modificació el 2016-10-04

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