Upregulation of GLUT1 expression is necessary for hypertrophy and survival of neonatal rat cardiomyocytes.
During hypertrophy the heart increases its utilization of glucose and decreases that of fatty acids, resuming a fetal pattern of substrate metabolism. As demonstrated here, GLUT1 protein expression is increased in association with in vivo pressure-overload-induced hypertrophy. The relationship of changes in GLUT1 to enhanced glucose uptake and to cardiomyocyte hypertrophy and survival is not known. To explore this question we first examined the effect of prostaglandin F2alpha (PGF2alpha), an established hypertrophic agonist, on GLUT1 expression and glucose uptake in neonatal rat ventricular myocytes (NRVMs). PGF2alpha treatment for 24 h led to a fivefold increase in GLUT1 expression and a sixfold increase in glucose uptake. However, NRVMs cultured in the absence of glucose or with 3-O-methyl glucose, a competitive inhibitor of glucose uptake, still exhibited PGF2alpha-induced hypertrophic growth. In addition, we determined that overexpression of GLUT1 using adenovirus was insufficient to cause an increase in cell size, myofibrillar organization, or atrial natriuretic factor (ANF) expression. On the other hand, adenoviral overexpression of antisense GLUT1 (which blocked PGF2alpha-induced increases in GLUT1 protein) prevented PGF2alpha-stimulated cell enlargement and increases in ANF transcription. Overexpression of GLUT1 or addition of PGF2alpha also protected cells against serum deprivation-induced apoptosis; this effect was blocked by antisense GLUT1 but, surprisingly, was not dependent on glucose. Together, these data suggest that upregulation of GLUT1 serves a role in agonist-induced hypertrophy and survival which can be dissociated from its role in glucose transport.
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000473:pathology; D017209:Apoptosis; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D001692:Biological Transport; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D015237:Dinoprost / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D006984:Hypertrophy; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000378:metabolism; D032342:Muscle Cells / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions; D013997:Time Factors; D015854:Up-Regulation
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D016376:Oligonucleotides, Antisense; C495678:Slc2a1 protein, mouse; C495679:Slc2a1 protein, rat; D009320:Atrial Natriuretic Factor; D015237:Dinoprost; D005947:Glucose