Non-carrier-mediated uptake of the mannosidase I inhibitor 1-deoxymannojirimycin by K562 erythroleukemic cells

J Biol Chem. 1989 Jun 15;264(17):10271-5.

Abstract

A 3H label was introduced at the C-1 position of the mannosidase I inhibitor 1-deoxymannojirimycin (dMM) by catalytic hydrogenolysis of benzyl-2,3-O-isopropylidene-5-N-benzyl-6-O-benzyl-alpha-D-mannofurano side with 3H2. 1-[3H]dMM as well as its precursor 1-[3H]2,3-O-isopropylidene-dMM had identical Rf as the nonradioactive compounds on TLC. Furthermore, alpha 1-antitrypsin secreted by HepG2 cells was modified indistinguishably by treatment of the cells with dMM and 1-[3H]dMM. Thus, 1-[3H]dMM had chemical and biological properties identical with authentic dMM. Uptake of [14C]mannose by K562 cells could be inhibited by glucose but not by the mannose analogue dMM. Thus, dMM does not enter the cell through hexose transporter(s). Uptake of 1-[3H]dMM by K562 cells could not be inhibited by increasing concentrations of nonradioactive dMM (from 1-32,000 microM), showing transport of dMM into cells through nonfacilitated diffusion. Furthermore, uptake of 1-[3H]dMM by K562 cells was observed at 0 degrees C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin
  • Biological Transport / drug effects
  • Cell Line
  • Glucosamine / analogs & derivatives
  • Glucosamine / metabolism
  • Glucose / pharmacology
  • Humans
  • Kinetics
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Mannose / metabolism
  • Mannosidases / antagonists & inhibitors*
  • Tritium

Substances

  • Tritium
  • 1-Deoxynojirimycin
  • Mannosidases
  • mannosyl-oligosaccharide 1,2-alpha-mannosidase
  • Glucose
  • Glucosamine
  • Mannose