Resistance to apoptosis in Fanconi's anaemia

FEBS Letters

Franceschi, Claudio³  Malorni, Walter⁴  Zatterale, Adriana¹  Macchioni, Sabrina³  Calzone, Rita¹  Cossarizza, Andrea³  Guido, Marcello³  Straface, Elisabetta⁴  Monti, Daniela³  Pagano, Giovanni² 

[1]Elena d'Aosta Hospital, Cytogenetic Service, Via Cagnazzi 29, 80136 Naples, Italy

[2]Italian National Cancer Institute, Via M. Semmola, 80131 Naples, Italy

[3]Department of Biomedical Sciences, Section General Pathology, University of Modena, Via Campi 287, 41100 Modena, Italy

[4]Department of Ultrastructures, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy

关键词: Fanconi's anaemia;    Apoptosis;    Mitochondria;    Deoxy-d-ribose;    2-;    Tumour necrosis factor-α;    FA;    Fanconi's anaemia;    PBMC;    peripheral blood mononuclear cell(s);    dRib;    2-deoxy-d-ribose;    TNF-α;    tumour necrosis factor-α;    CHX;    cycloheximide;    MMP;    mitochondrial membrane potential;    NAC;    N-acetylcysteine;    DEB;    diepoxybutane;    MMC;    mitomycin C;    ROS;    reactive oxygen species;    TdT;    terminal deoxynucleotidyl transferase;    TUNEL;    TdT-mediated dUTP nick end labeling;    PI;    propidium iodide;    JC-1;    5;    5′;    6;    6′-tetrachloro-1;    1′;    3;    3′-tetraethylbenzimidazolcarbocyanine iodide;   

DOI  :  10.1016/S0014-5793(97)00550-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Fanconi's anaemia (FA) is a rare autosomal recessive disease characterised by progressive pancytopoenia, a diverse assortment of congenital malformations, an increased sensitivity to reactive oxygen species and a predisposition to the development of malignancies. In the present study, we assessed the propensity to undergo apoptosis of peripheral blood mononuclear cells (PBMC) from Italian FA patients. Cells were challenged by 2-deoxy-d-ribose (dRib) or TNF-α plus cycloheximide as agents that induce apoptosis by interfering with cell redox status and mitochondrial membrane potential (MMP), and PBMC from FA patients resulted to be less prone to die than those from healthy subjects. The decreased susceptibility of FA cells to undergo apoptosis was also evident when another parameter highly correlated with the apoptotic process, i.e. MMP, was measured. Moreover, when N-acetylcysteine was added to dRib-treated PBMC, a strong protection was evident either in PBMC from control subjects or from FA patients. These data indicate that an alteration of unknown nature of the mechanisms favouring apoptosis is present in freshly collected cells from FA patients, and that such alteration could contribute to the pathogenesis of the disease, and particularly to the increased susceptibility to cancer.

【 授权许可】

Unknown