Studies of renal injury. II. Activation of the glucose transporter 1 (GLUT1) gene and glycolysis in LLC-PK1 cells under Ca2+ stress.
Injury to the renal proximal tubule is common and may be followed by either recovery or cell death. The survival of injured cells is supported by a transient change in cellular metabolism that maintains life even when oxygen tension is reduced. This adaptive process involves the activation of the gene encoding the glucose transporter GLUT1, which is essential to maintain the high rates of glucose influx demanded by glycolysis. We hypothesized that after cell injury increases of cell Ca2+ (Ca2+i) initiate the flow of information that culminates with the upregulation of the stress response gene GLUT1. We found that elevations of Ca2+i caused by the calcium ionophore A23187 activated the expression of the GLUT1 gene in LLC-PK1 cells. The stimulatory effect of Ca2+i on GLUT1 gene expression was, at least in part, transcriptional and resulted in higher levels of GLUT1 mRNA, cognate protein, cellular hexose transport activity, glucose consumption, and lactate production. This response was vital to the renal cells, as its interruption severely increased Ca2+-induced cytotoxicity and cell mortality. We propose that increases of Ca2+i initiate stress responses, represented in part by activation of the GLUT1 gene, and that disruption to the flow of information originating from Ca2+-induced stress, or to the coordinated expression of the stress response, prevents cell recovery after injury and may be an important cause of permanent renal cell injury and cell death.
Dominguez
J H
JH
Department of Medicine, Indiana University Medical Center, Indiana 46202, USA.
Song
B
B
Liu-Chen
S
S
Qulali
M
M
Howard
R
R
Lee
C H
CH
McAteer
J
J
D058186:Acute Kidney Injury; D000818:Animals; D001692:Biological Transport; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D007687:Kidney Tubules, Proximal / Q000293:injuries* / Q000378:metabolism; D007700:Kinetics; D018374:LLC-PK1 Cells; D007773:Lactates / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013552:Swine; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis
D051272:Glucose Transporter Type 1; D007773:Lactates; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000001:Calcimycin; D003847:Deoxyglucose; D015500:Chloramphenicol O-Acetyltransferase; D001616:beta-Galactosidase; D005947:Glucose; D002118:Calcium