The long-term effects of anti-retroviral protease inhibitors on sugar transport in L6 cells.
The objective of this study was to investigate the long-term effects of anti-retroviral protease inhibitors (PIs) on 2-deoxy-d -glucose (2-DG) transport in L6 cells in vitro. Exposure of L6 cells to saquinavir, ritonavir, indinavir and amprenavir resulted in significant increases in 2-DG transport using PI concentrations of 1-10 microM with continual exposure to PI. After removal of the PI for up to 48 h, 2-DG transport increases did not change and remained at pre-reversal levels. These changes in 2-DG transport were not related to stress-induced sugar transport or to apoptosis. The examination of glucose transporter (GLUT) 1, 3 or 4 translocation with subcellular fractionation indicated that insulin (i.e. 67 nM) could induce the translocation of all the GLUTs to the plasma membrane. Also, ritonavir (10 microM), which leads to a 2-fold increase in 2-DG transport, demonstrated increased GLUT (i.e. 1, 3 or 4) presence in the plasma membrane fraction, in the presence or absence of insulin. This increased 2-DG transport involved transporter presence in plasma membrane preparations and did not affect the ability of insulin to stimulate 2-DG transport with continual PI exposure. The mechanism(s) involved indicates ready reversibility of PI effects on transporters. The mechanism(s) why reversibility of PI-induced 2-DG transport was similar plus or minus PI was not apparent.
Germinario
R J
RJ
Lady Davis Institute for Medical Research, SMBD Jewish General Hospital, 3755 Cote St Catherine Road, Montreal, Quebec, Canada. ralph.germinario@mcgill.ca
Colby-Germinario
S P
SP
Cammalleri
C
C
Wainberg
M A
MA
D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D002219:Carbamates; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism*; D005663:Furans; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D019438:Ritonavir / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D002219:Carbamates; D005663:Furans; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D017320:HIV Protease Inhibitors; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; C495692:SLC2A4 protein, human; D013449:Sulfonamides; C095108:amprenavir; D019469:Indinavir; D003847:Deoxyglucose; D019258:Saquinavir; D019438:Ritonavir