Vassord Camille, Lapouméroulie Claudine, Koumaravelou Kailasam, Srivastava Alok, Krishnamoorthy Rajagopal
Inserm, U763 Hôpital Robert Debré, Paris, France.
Eur J Haematol. 2008 Apr;80(4):299-302. doi: 10.1111/j.1600-0609.2008.01031.x. Epub 2008 Jan 14.
Busulfan-mediated endothelial damage is believed to be a common mechanism in a variety of vascular disorders that occur during haematopoietic stem cell transplantation. The alkylating capacity of busulfan is compromised in vivo by enzymatic conjugation with glutathione, principally catalysed by glutathione S-transferase alpha (GST alpha). We investigated whether the susceptibility of endothelial cells to busulfan-mediated damage is related to their intrinsic deficiency in GST alpha expression. We tested for the expression of GST alpha mRNA by real-time quantitative PCR and the GST protein by enzyme-linked immunosorbent assay in various independently derived endothelial cell types (human bone marrow-derived endothelial cell line and endothelial cells from human vein umbilical cord ) and in a control hepatic cell line, HepG2. We demonstrate that endothelial cells, contrary to hepatic cells do not express GST alpha either at mRNA or protein levels and hence are potentially susceptible to busulfan-mediated cytotoxic damage.
白消安介导的内皮损伤被认为是造血干细胞移植期间发生的各种血管疾病的常见机制。在体内,白消安的烷基化能力会因与谷胱甘肽的酶促结合而受损,这一过程主要由谷胱甘肽S-转移酶α(GSTα)催化。我们研究了内皮细胞对白消安介导损伤的易感性是否与其GSTα表达的内在缺陷有关。我们通过实时定量PCR检测了GSTα mRNA的表达,并通过酶联免疫吸附测定法检测了各种独立来源的内皮细胞类型(人骨髓来源的内皮细胞系和人脐静脉内皮细胞)以及对照肝细胞系HepG2中GST蛋白的表达。我们证明,与肝细胞相反,内皮细胞在mRNA或蛋白质水平上均不表达GSTα,因此可能对白消安介导的细胞毒性损伤敏感。