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BIOLOGICHESKIE MEMBRANY

Journal of Membrane and Cell Biology

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Myeloid Differentiation Increases Resistance of Leukemic Cells to TRAIL-Induced Death by Reducing the Expression of DR4 and DR5 Receptors

Ya. V. Lomovskaya, M. I. Kobyakova, R. S. Fadeev

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology. 2023;17(1):43-57

Pages: 43-57

Abstract

The Glycoprotein VI (GPVI) receptor is the primary signaling receptor for collagen on the platelet surface, playing a critical role in hemostasis and thrombosis. While GPVI-mediated platelet activation is a fundamental process in cell biology, significant inter-individual variability in the resulting functional response is frequently observed. This study investigated the molecular and cellular basis for this variability by analyzing key indicators of platelet activation following stimulation with a GPVI-specific agonist. Using flow cytometry and calcium imaging techniques, we quantified the concentration of cytosolic Ca²⁺ and the degree of P-selectin expression, a marker of granule secretion, in platelets from a cohort of healthy donors. Our results demonstrate a wide range of maximum Ca²⁺ flux and P-selectin expression levels, even under standardized conditions. Furthermore, we found that the variability in the functional response correlates with differences in the basal expression level of GPVI on the platelet membrane. These findings suggest that GPVI surface density is a major determinant of platelet reactivity, providing a potential biomarker for assessing individual thrombotic risk and guiding antiplatelet therapy.

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