Stimulation of glut1 glucose transporter expression in response to
exposure to the calcium ionophore a23187.
Mitani, Yasuo, Alireza Behrooz, George R. Dubyak, and Faramarz Ismail
-Beigi.
Departments of Medicine, and of Physiology and Biophysics, Division
of Clinical and Molecular Endocrinology, Case Western Reserve
University, Cleveland, Ohio 44106-4951
APStracts 2:0210C, 1995.
We tested the hypothesis that an increase in cytosolic calcium
concentration stimulates GLUT1 gene expression. Exposure of a rat
liver cell line (Clone 9) to 3 [mu]M A23187 for 12 h resulted in 3-,
5-, and 10-fold increases in cytochalasin B-inhibitable 3-O
-methyglucose transport, GLUT1 protein, and GLUT1 mRNA content,
respectively. The induction of GLUT1 mRNA in response to A23187 is
not preceded by a significant decrease in cell ATP content. This
induction is prevented by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
-tetraacetic acid (BAPTA) in conjunction with EGTA. To investigate the
mechanism of GLUT1 mRNA induction, we found that exposure to A23187
stabilized GLUT1 mRNA: employing actinomycin D, GLUT1 mRNA had a half
life of 1.5 and 5.5 h in control and A23187-treated cells,
respectively. In nuclear run-on assays, the rate of GLUT1 gene
transcription was stimulated 1.5 to 1.7-fold in nuclei isolated from
cells exposed to A23187 for either 30 min or 2 h. These results
demonstrate that exposure to A23187 stimulates GLUT1 gene expression,
and that the increase in GLUT1 mRNA content is mediated in part by
enhanced GLUT1 gene transcription as well as decreased GLUT1 mRNA
degradation. The increase in GLUT1 mRNA content, in turn, is
associated with increased cell GLUT1 content and enhanced glucose
transport.
Received 7 April 1995; accepted in final form 12 May 1995.
APS Manuscript Number C209-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.