NAD(P)H: quinone oxidoreductase 1 expression in human bone marrow endothelial cells.
NAD(P)H:quinone oxidoreductase 1 (NQO1) participates in the detoxification of many environmental quinones and related compounds. Recent studies have suggested that individuals with a polymorphism in NQO1 (NQO1*2), which results in a decrease (heterozygous, NQO1*1/*2) or a total loss (homozygous, NQO1*2/*2) of NQO1, may be at increased risk for the development of leukemias. Previous studies have failed to detect NQO1 in freshly aspirated bone marrow including Ficoll-purified mononuclear cells and purified CD34(+) hematopoietic progenitor stem cells. In these studies we examined human bone marrow core biopsies by immunohistochemistry using monoclonal antibodies directed against NQO1. These studies revealed that NQO1 was expressed in human bone marrow but expression of NQO1 was limited to bone marrow endothelium and adipocytes. To confirm the expression of NQO1 in bone marrow endothelial cells we examined an immortalized human bone marrow endothelial cell line (HBMEC-60) for NQO1 protein expression. Immunoblot analysis and an activity assay confirmed the expression of NQO1 in HBMEC-60. These data demonstrate that NQO1 is present in human bone marrow. The increased risk of leukemia associated with a deficit in NQO1 levels due to the NQO1*2 polymorphism may reflect impaired quinone detoxification and an increased susceptibility of endothelial cells in bone marrow to environmental insults.
Siegel
D
D
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Ryder
J
J
Ross
D
D
D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic
D016660:NAD(P)H Dehydrogenase (Quinone)