Alpha-tocopherol is known to inhibit platelet aggregation but the mechanism responsible for this has not been elucidated. Glycoprotein IIb (GPIIb) is the α-subunit of the platelet membrane protein GPIIb/IIIa, which functions as a specific receptor for platelet aggregation. Human erythroleukemia (HEL) cells are megakaryocytelike and express the megakaryocyte-specific GPIIb gene. To understand the molecular mechanism of α-tocopherol on antiaggregation, we analyzed the effect of physiologically relevant concentrations of α-tocopherol on the expression of human GPIIb promoter in HEL cells. The enhancement of tetradecanoylphoerbol-12,13-acetate (TPA)-mediated transient and optimal expression of plasmids was achieved by adding 10-7-M TPA in the medium 24 h before lipofection. Transient expression of GPIIb promoter was determined in transfected cells pretreated with various concentrations of α-tocopherol. Our data shows that the GPIIb promoter activity was downregulated to 55, 23, 27, 20, and 15% in the presence of 10, 20, 40, 80, and 120 μg/ml of α-tocopherol, respectively, as compared with that in the absence of α-tocopherol. The downregulation of α-tocopherol on the TPA-mediated GPIIb promoter activity may result in a reduction of GPIIb protein expression and thus contribute to antiplatelet aggregation. Copyright (C) 2000 Elsevier Science Inc.
All Science Journal Classification (ASJC) codes
- Clinical Biochemistry