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 by endocytosis. When swainsonine is withdrawn from the culture medium, there is a decrease with time of cell-associated swainsonine. The kinetics of uptake and release of swainsonine and its slightly basic nature make it likely that swainsonine is concentrated initially in the lysosomes. This rapid, but reversible, concentration of swainsonine in lysosomes would be consistent with the observed effects of the toxin in vivo.
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Front Vet Sci
January 2025
State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems, College of Pastoral Agriculture Science and Technology, Engineering Research Center of Grassland Industry, Ministry of Education, Lanzhou University, Lanzhou, China.
Introduction: Standing milkvetch () is widely distributed in the wild in Eurasia and North America and has been bred for cultivated forage in China. Yellow stunt and root rot disease caused by is the primary disease of standing milkvetch. promotes the production of swainsonine in the plant.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:
Six C-6 fluorinated d-swainsonine derivatives and their enantiomers have been designed based on initial docking calculations, and synthesized from enantiomeric ribose-derived aldehydes, respectively. Glycosidase inhibition assay of these derivatives with d-swainsonine (1) and l-swainsonine (ent-1) as contrasts found that the C-6 fluorinated d-swainsonine derivatives with C-8 configurations as R (α) showed specific and potent inhibitions of jack bean α-mannosidase (model enzyme of Golgi α-mannosidase II); whereas their enantiomers with C-8 configurations as S (β) were powerful and selective α-l-rhamnosidase inhibitors. Molecular docking calculations found the C-6 fluorinatedd-swainsonine derivatives 21, 24 and 25 with highly coincident binding conformations with d-swainsonine (1) in their interactions with the active site of α-mannosidase (PDB ID: 1HWW).
View Article and Find Full Text PDFEquine Vet J
November 2024
Lehrstuhl für Tierernährung und Diätetik, Ludwig-Maximilians-Universität München, Munich, Germany.
Background: While previous reports come mostly from the southern Americas, several outbreaks of hypersalivation in horses were observed in Middle Europe from 2016 to 2018.
Objective: To describe feed-induced hypersalivation in European horses.
Study Design: Analysis of feedstuffs.
Sheng Wu Gong Cheng Xue Bao
October 2024
College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
In order to mitigate the adverse effects of madrassa poisoning disease on our livestock industry and to fully utilize the potential pasture resources, biodegradation of locoweed can remove swainsonine, the major toxic component of locoweed, so that the locoweed can be used as high-quality forage. HW08 can stably and efficiently degrade swainsonine. In this study, , as a food-grade microorganism, was used as a vector to express four key degradation genes from .
View Article and Find Full Text PDFMicroorganisms
October 2024
College of Life Science and Technology, Inner Mongolia Normal University, Hohhot 010022, China.
The gene in the endophytic fungus OW 7.8 isolated from was identified, and the gene knockout mutant Δ was first constructed in this study. Compared with OW 7.
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