The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins.
In mammals, glucose transport is mediated by five structurally related glucose transporters that show a characteristic cell-specific expression. However, the rat brain/HepG2/erythrocyte-type glucose transporter GLUT-1 is expressed at low levels in most cells. The reason for this coexpression is not clear. GLUT-1 is negatively regulated by glucose. Another family of proteins, glucose-regulated proteins (GRPs), is also ubiquitously expressed and stimulated by glucose deprivation and other cellular stresses. We therefore hypothesized that GLUT-1 may be a glucose-regulated stress protein. This was tested by subjecting L8 myocytes and NIH 3T3 fibroblasts to glucose starvation or exposure to the calcium ionophore A23187, 2-mercaptoethanol, or tunicamycin, all known to increase GRP levels. The mRNA for GLUT-1 was augmented by 50-300% in a time-dependent manner, similarly to the changes in GRP-78 mRNA. Ex vivo incubation of rat soleus muscles induced a marked and concomitant rise in the mRNA levels of GLUT-1 and GRP-78. Finally, calcium ionophore A23187 and 2-mercaptoethanol induced a 2- to 3-fold increase in the levels of the GLUT-1 protein and hexose uptake. In all instances in which GRP-78 and GLUT-1 responded to stress, the transcription of the cell-specific muscle/adipocyte-type insulin-responsive glucose transporter (GLUT-4) did not change. Thus, despite the lack of structural similarity, GLUT-1 and GRP-78 expression is regulated similarly, whereas the regulation of GLUT-4, which is structurally related to GLUT-1, is different. We propose that GLUT-1 belongs to the GRP family of stress proteins and that its ubiquitous expression may serve a specific purpose during cellular stress.
Wertheimer
E
E
Department of Endocrinology and Metabolism, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Sasson
S
S
Cerasi
E
E
Ben-Neriah
Y
Y
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics*; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009132:Muscles; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D014415:Tunicamycin / Q000494:pharmacology
D006360:Heat-Shock Proteins; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D014415:Tunicamycin; D000001:Calcimycin; D012313:RNA; D005947:Glucose