Hexose transport in human myoblasts.
The present investigation reports on the hexose transport properties of human myoblasts isolated from normal subjects and from patients with Duchenne muscular dystrophy (DMD). Similar to rat myoblast L6, normal human myoblasts possess a high- (HAHT) and a low- (LAHT) affinity hexose transport system. The non-metabolizable hexose analogue, 2-deoxyglucose, is preferentially taken up by HAHT. The transport of this analogue is the rate-limiting step in the uptake process. This human myoblast HAHT is also similar to that of the rat myoblast in its substrate specificity and in response to the energy uncouplers, cytochalasin B and phloretin. The human myoblast LAHT resembles that of rat myoblast in its insensitivity to energy uncouplers, and in its transport affinity and capacity for 3-O-methyl-D-glucose. Although DMD myoblasts resemble their normal counterpart in their ability to differentiate, they differ significantly in their hexose transport properties. In addition to HAHT and LAHT present in normal human myoblast, DMD myoblasts contain a super-high-affinity hexose transport system (SHAHT). SHAHT can be detected only at very low substrate concentrations. It differs from HAHT not only in its much higher transport affinity, but also in its response to the traditional hexose transport inhibitors. For example, SHAHT can be activated by cytochalasin B and phlorizin, whereas it is more sensitive to inhibition by phloretin. Unlike HAHT, energy uncouplers are found to be ineffective in inhibiting SHAHT. It should be mentioned that SHAHT cannot be detected in myoblasts isolated from patients with other types of myopathy. The present study serves to demonstrate that more than one hexose transport system is operating in human skeletal muscle cells, as found in other cell types.
Mesmer
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Department of Biochemistry, University of Western Ontario, London, Canada.
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D019297:2,4-Dinitrophenol; D019325:3-O-Methylglucose; D001693:Biological Transport, Active / Q000187:drug effects; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003837:Deoxy Sugars / Q000493:pharmacokinetics*; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004140:Dinitrophenols / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008757:Methylglucosides / Q000493:pharmacokinetics; D009132:Muscles / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology
D003837:Deoxy Sugars; D004140:Dinitrophenols; D008757:Methylglucosides; D019325:3-O-Methylglucose; D003571:Cytochalasin B; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D003847:Deoxyglucose; D010695:Phlorhizin; D019297:2,4-Dinitrophenol; D010693:Phloretin