Endothelial cells do not express GSTA1: potential relevance to busulfan-mediated endothelial damage during haematopoietic stem cell transplantation.
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.
Vassord
Camille
C
Inserm, U763 Hôpital Robert Debré, Paris, France.
Lapouméroulie
Claudine
C
Koumaravelou
Kailasam
K
Srivastava
Alok
A
Krishnamoorthy
Rajagopal
R
D002066:Busulfan / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics
C484555:GSTA1 protein, human; D005982:Glutathione Transferase; D002066:Busulfan