Uncouplers of oxidative phosphorylation promote derepression of the hexose transport system in cultures of hamster cells.
Long-term (18-24 hr) preincubation of NIL hamster cell cultures with D-glucose or D-glucosamine (both of which repress the hexose transport system) gave rise to a striking loss of the hexose transport system ("super-repression") when cycloheximide was also present in the culture medium. However, if 0.2 mM 2,4-dinitrophenol (DNP) was also present, the cycloheximide-mediated super-repression was prevented. Moreover, the presence of DNP at this low concentration contributed to an increase in hexose uptake such that it was substantially higher than that permitted by either of the two repressive sugars alone. When the cultures were maintained in medium containing D-fructose in place of glucose, a marked increase in uptake occurred, and this increase (derepression) was not affected by DNP. The derepression due to glucose deprivation and the increases caused by DNP treatment were also observed when 3-O-methylglucose was used to measure hexose transport. Although cultures maintained in the presence of glucosamine exhibited a repressed hexose transport rate, they did not generate significant amounts of lactic acid. DNP, and other uncouplers of oxidative phosphorylation, promoted a derepressed state of hexose transport but did not stimulate the generation of lactate from glucosamine. These data suggest that the metabolic repression phenomena of hexose transport do not depend on glycolysis but rather on the "energized" state of the cell. The energized state of the cell may also be required for the super-repression of hexose transport that is especially apparent when protein synthesis is blocked by cycloheximide.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004140:Dinitrophenols / Q000494:pharmacology; D005690:Galactose / Q000378:metabolism; D005944:Glucosamine / Q000037:antagonists & inhibitors; D005947:Glucose / Q000037:antagonists & inhibitors; D006601:Hexoses / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014475:Uncoupling Agents / Q000494:pharmacology*
D004140:Dinitrophenols; D006601:Hexoses; D009840:Oligomycins; D014475:Uncoupling Agents; D005947:Glucose; D005944:Glucosamine; D005690:Galactose