The uptake of swainsonine, a specific inhibitor of alpha-D-mannosidase, into normal human fibroblasts in culture

Journal of Cellular Biochemistry
K ChotaiP R Dorling

Abstract

Swainsonine, an indolizidine alkaloid, found in plants of the genus Swainsona, has been shown to be a strong inhibitor in vitro of the alpha-D-mannosidase activity in normal human fibroblasts. Therefore, inhibition of alpha-D-mannosidase activity in extracts of harvested cells grown with swainsonine in the medium has been used to follow the association of the alkaloid with normal human fibroblasts in culture. Swainsonine that could not be removed by extensive washing became associated with the cells within 1 min, and it is concluded that the alkaloid is internalized rapidly by the cells. The amount of swainsonine taken up into the cells depended on the length of time in contact and the concentration of swainsonine in the medium, but at 37 degrees C a plateau of internalized swainsonine occurred after 2 hr with extracellular concentrations of swainsonine of 100 microM or greater. At lower concentrations of swainsonine the rate of uptake was found to be temperature-dependent, increasing greatly at 20 degrees C. The rapidity and temperature sensitivity of the uptake, together with the observation that mannose or mannose-6-phosphate did not prevent the association, suggest that swainsonine enters the cells by permeation rather than...Continue Reading

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Citations

Jun 12, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Chao LiShouju Li
May 1, 1984·Archives of Biochemistry and Biophysics·R SaulA D Elbein
Nov 15, 1983·Biochemical and Biophysical Research Communications·R G Arumugham, M L Tanzer
Apr 25, 2019·Journal of Medicinal Chemistry·Rocío Rísquez-CuadroCarmen Ortiz Mellet
Aug 9, 2003·Journal of Agricultural and Food Chemistry·Mitsue HaraguchiNaoki Asano
Mar 18, 2005·Journal of Medicinal Chemistry·Atsushi KatoNaoki Asano

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