Studies of renal injury. I. Gentamicin toxicity and expression of basolateral transporters

Jesus Dominguez, Calvin C. Hale, Mona Qulali

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 l (GLUT1) and csubunit of Na- -KATPase (a,-NKA) in renal tubules. The products of these genes mediate Na"-dependent Ca2' efflux, glucose efflux and influx, and ATP-dependent Naf efflux across tubular basolateral membranes, respectively. After 10 days of gentamicin intoxication (40 mg/kg ip, twice daily), levels of mRNAs encoding NaCaX and the cognate protein declined. GLUT1 mRNA levels increased, although GLUT1 protein levels were also reduced. Moreover, whereas cq-NKA mRNA levels remained unchanged, arNKA 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 diminish the possibility of recovery in gentamicin intoxication.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume270
Issue number2 PART 2
StatePublished - 1996

Fingerprint

Gentamicins
Kidney
Messenger RNA
Wounds and Injuries
Proteins
Glucose Transporter Type 1
Gene Expression
Proximal Kidney Tubule
Facilitative Glucose Transport Proteins
Genes
Adenosine Triphosphate
Glucose
Membranes

Keywords

  • Acute renal failure
  • Calcium
  • Stress response

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Studies of renal injury. I. Gentamicin toxicity and expression of basolateral transporters. / Dominguez, Jesus; Hale, Calvin C.; Qulali, Mona.

In: American Journal of Physiology - Renal Physiology, Vol. 270, No. 2 PART 2, 1996.

Research output: Contribution to journalArticle

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