AJP - Cell Physiology, Vol 270, Issue 1 C235-C242, Copyright © 1996 by American Physiological Society

ARTICLES

Induction of GLUT-1 mRNA in response to inhibition of oxidative phosphorylation: role of increased [Ca2+]i

Y. Mitani, G. R. Dubyak and F. Ismail-Beigi
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4951, USA.

Exposure of Clone 9 cells (a rat liver cell line expressing only the GLUT-1 isoform) to 5 mM azide or to 3 microM ionomycin for 12 h results in 3.7 +/- 0.3- and 4.9 +/- 0.4-fold increases in GLUT-1 mRNA content, respectively, suggesting the hypothesis that a rise in cytosolic free calcium concentration ([Ca2+]i) mediates the induction of GLUT-1 mRNA by azide. Five lines of evidence were employed to test this hypothesis. 1) Exposure of cells to 0-3 microM of ionomycin increased [Ca2+]i from 83 +/- 9 to 504 +/- 20 nM (half-maximal effect at 0.1 microM ionomycin), whereas half-maximal increase in GLUT-1 mRNA occurred at 1 microM ionomycin, with the increase in the mRNA being negligible at [Ca2+]i below 400 nM. Exposure of cells to 5 mM azide, however, increased [Ca2+]i to maximal value of 174 +/- 22 nM at 15 s, suggesting that the magnitude of the increase in [Ca2+]i by azide may not be adequate for the response. 2) The increase in GLUT-1 mRNA content by azide was fully preserved in cells preloaded with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). 3) GLUT-1 mRNA content increased within 30 min of exposure to ionomycin, whereas the mRNA increased after a "delay" period of 2 h in cells exposed to 5 mM azide. 4) A brief (2-min) rise in [Ca2+]i by ionomycin was sufficient to increase GLUT-1 mRNA content, whereas continuous exposure to azide for > 1 h was necessary for a subsequent induction of the mRNA. 5) Treatment with ionomycin, A-23187, and thapsigargin caused larger increases in glucose-regulated protein 78 and 94 and in 70-kDa heat shock protein mRNAs than in GLUT-1 mRNA, whereas treatment with azide resulted in greater induction of GLUT-1 mRNA. These results strongly suggest that, whereas increased [Ca2+]i enhances GLUT-1 mRNA expression and azide increases [Ca2+]i, the rise in [Ca2+]i does not mediate the induction of GLUT-1 mRNA in response to inhibition of oxidative phosphorylation.

This article has been cited by other articles:

				M. Jing, V. K Cheruvu, and F. Ismail-Beigi Stimulation of glucose transport in response to activation of distinct AMPK signaling pathways Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1071 - C1082. [Abstract] [Full Text] [PDF]

				M. Jing and F. Ismail-Beigi Critical role of 5'-AMP-activated protein kinase in the stimulation of glucose transport in response to inhibition of oxidative phosphorylation Am J Physiol Cell Physiol, January 1, 2007; 292(1): C477 - C487. [Abstract] [Full Text] [PDF]

				M. Jing and F. Ismail-Beigi Role of 5'-AMP-activated protein kinase in stimulation of glucose transport in response to inhibition of oxidative phosphorylation Am J Physiol Cell Physiol, February 1, 2006; 290(2): C484 - C491. [Abstract] [Full Text] [PDF]

				J. Li, M. Puceat, C. Perez-Terzic, A. Mery, K. Nakamura, M. Michalak, K.-H. Krause, and M. E. Jaconi Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis J. Cell Biol., July 8, 2002; 158(1): 103 - 113. [Abstract] [Full Text] [PDF]

				A. Behrooz and F. Ismail-Beigi Stimulation of Glucose Transport by Hypoxia: Signals and Mechanisms Physiology, June 1, 1999; 14(3): 105 - 110. [Abstract] [Full Text] [PDF]

				Z. A. Khayat, T. Tsakiridis, A. Ueyama, R. Somwar, Y. Ebina, and A. Klip Rapid stimulation of glucose transport by mitochondrial uncoupling depends in part on cytosolic Ca2+ and cPKC Am J Physiol Cell Physiol, December 1, 1998; 275(6): C1487 - C1497. [Abstract] [Full Text] [PDF]

				A. Behrooz and F. Ismail-Beigi Dual Control of glut1 Glucose Transporter Gene Expression by Hypoxia and by Inhibition of Oxidative Phosphorylation J. Biol. Chem., February 28, 1997; 272(9): 5555 - 5562. [Abstract] [Full Text] [PDF]