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- W4229804903 abstract "Intracellular protein transport in endothelial cells is selectively inhibited by homocysteine, a thiol amino acid associated with both thrombosis and atherosclerosis. In a previous study, homocysteine decreased cell surface expression of the surface transmembrane glycoprotein thrombomodulin without decreasing secretion of another endothelial cell protein, plasminogen activator inhibitor-1. To define further the effects of homocysteine on protein transport, we examined the processing and secretion of the multimeric glycoprotein von Willebrand factor (vWF) in human umbilical vein endothelial cells. Incubation with 2 mmol/L homocysteine resulted in complete loss of vWF multimers and prevented asparagine-linked oligosaccharide maturation, propeptide cleavage, and secretion; these effects are consistent with impaired exit from the endoplasmic reticulum (ER). Dimerization was only partially inhibited, suggesting that homocysteine causes retention of provWF in the ER without preventing dimer formation. In pulse-chase incubations, intracellular provWF was degraded before exiting the ER in homocysteine-treated cells. Homocysteine also inhibited the processing and secretion of a carboxyl-terminal truncation mutant of human provWF expressed in rat insulinoma cells, indicating that retention in the endoplasmic reticulum can be mediated by regions of provWF apart from the carboxyl-terminal 20-Kd segment. These results suggest that retention of secretory proteins in the ER is regulated by redox mechanisms and imply that the intracellular transport of multiple endothelial cell proteins may be altered in patients with homocystinuria." @default.
- W4229804903 created "2022-05-11" @default.
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- W4229804903 date "1993-02-01" @default.
- W4229804903 modified "2023-10-14" @default.
- W4229804903 title "Homocysteine inhibits von Willebrand factor processing and secretion by preventing transport from the endoplasmic reticulum" @default.
- W4229804903 doi "https://doi.org/10.1182/blood.v81.3.683.bloodjournal813683" @default.
- W4229804903 hasPublicationYear "1993" @default.
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