Studies of renal injury i. gentamicin toxicity and the expression
of genes encoding basolateral transporters of rat renal proximal
tubules.
Dominguez, Jesus H., Calvin C. Hale, and Mona Qulali.
Department of Medicine, Department of Physiology and Biophysics,
Indiana University Medical Center and Veterans Administration Medical
Center, Indianapolis, Indiana 46202; and Department of Veterinarian
Medical Sciences, John M. Dalton Research Center, University of
Missouri, Columbia, Missouri 65211
APStracts 2:0129F, 1995.
Gentamicin nephrotoxicity may arise in part from alterations in the
expression of genes critical for renal proximal tubule metabolism. We
tested the hypothesis that gentamicin suppressed the gene expression
of the Na+/Ca2+ exchanger (NaCaX), glucose transporter 1 (GLUT1) and
1 subunit of Na+/K+ ATPase (1 NKA) in renal tubules. The products of
these genes mediate Na+-dependent Ca2+ efflux, glucose efflux and
influx, and ATP-dependent Na+ efflux across tubular basolateral
membranes, respectively. After 10 days of gentamicin intoxication (40
mg/kg/twice daily, I.P.), levels of mRNAs encoding NaCaX and the
cognate protein declined. GLUT1 mRNA levels increased, although GLUT1
protein levels were also reduced. Moreover, whereas [alpha]1 NKA mRNA
levels remained unchanged, [alpha]1 NKA protein levels were also
reduced. We suggest that the higher GLUT1 mRNA level is part of the
stress response to tubular injury. However, regardless of the mRNA
level, the most consistent effect of gentamicin was reduction of
specific protein levels. We propose that failure to translate high
levels of mRNA into proportionally high levels of protein, as in the
case of GLUT1, may attenuate the expression of stress response gene
products; and thus diminsh the possibility of recovery in gentamicin
intoxication.
Received 18 October 1994; accepted in final form 17 July 1995.
APS Manuscript Number F376-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.