Paradoxical effects of cycloheximide and cytochalasin B on hamster cell hexose uptake.

Abstract

Cellular regulation of hexose uptake was studied in cultures of NIL hamster [embryo fibroblast] cells. Enhancements of galactose uptake were elicited most strikingly by maintaining confluent NIL cultures in culture media devoid of glucose. These glucose-starved cultures showed up to 8- or 9-fold enhancements in the galactose uptake test. When these cultures were treated for extended periods with cycloheximide, the enhanced uptake was left unimparied, whereas the uptake by glucose-fed cells, similarly treated with cycloheximide, was inhibited greater than 90%. Addition of glucose to these starved cultures resulted in a gradual decline of uptake rates to the unenhanced level (t1/2 [half-life] approximately 3 h). When both glucose and cycloheximide were added simultaneously, the decline was arrested for at least 12 h. If cytochalasin B (the specific inhibitor of hexose transport) was present, the uptake of galactose by both starved and fed cells was close to completely inhibited. By several criteria, cells maintained for 24 h in medium containing both glucose and cytochalasin B were glucose-fed. Yet, when the cytochalasin B was removed, the cells had enhanced rates of galactose uptake. The regulation of the hexose uptake system may therefore not be guided by the levels of glucose catabolites. Alternative mechanisms that may control hexose uptake are considered.