人类范科尼贫血A细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的细胞凋亡敏感。

Human Fanconi A cells are susceptible to TRAIL-induced apoptosis.

作者信息

Pigullo Simona, Ferretti Elisa, Lanciotti Marina, Bruschi Maurizio, Candiano Giovanni, Svahn Johanna, Haneline Laura, Dufour Carlo, Pistoia Vito, Corcione Anna

机构信息

Haematology Unit, Department of Paediatric Haemato-Oncology, G. Gaslini Children's Hospital, Genoa, Italy.

出版信息

Br J Haematol. 2007 Jan;136(2):315-8. doi: 10.1111/j.1365-2141.2006.06432.x.

DOI:10.1111/j.1365-2141.2006.06432.x

PMID:17233822

Abstract

Tumour necrosis factor (TNF) contributes to the pathogenesis of bone marrow failure in Fanconi anaemia (FA) patients. The sensitivity of haematopoietic cells from FA, complementation group A (FANCA) subjects, who represent the majority of FA patients, to TNF-related apoptosis-inducing ligand (TRAIL) is unknown. The human lymphoblastoid FANCA HSC072 cell line and the genetically corrected counterpart HSC072FANCA-neo were tested for apoptoptic response to TRAIL using flow cytometry and Western blotting. FANCA cells were more sensitive to TRAIL-induced apoptosis than their corrected counterparts, indicating that TRAIL negatively regulates haematopoietic FANCA cell lines. This effect involved poly(ADP-ribose) polymerase-1 cleavage and caspase-8 activation.

摘要

肿瘤坏死因子（TNF）促成范可尼贫血（FA）患者骨髓衰竭的发病机制。代表大多数FA患者的FA互补组A（FANCA）受试者的造血细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）的敏感性尚不清楚。使用流式细胞术和蛋白质印迹法检测了人类淋巴母细胞FANCA HSC072细胞系以及基因校正后的对应细胞系HSC072FANCA-neo对TRAIL的凋亡反应。FANCA细胞比其校正后的对应细胞对TRAIL诱导的凋亡更敏感，表明TRAIL对造血FANCA细胞系具有负调控作用。这种作用涉及聚（ADP-核糖）聚合酶-1的切割和半胱天冬酶-8的激活。