Feedback inhibition of aldose reductase gene expression in rat renal medulla. Galactitol accumulation enzyme reduces mRNA levels and depletes cellular inositol content

C. Bondy, B. D. Cowley, S. L. Lightman, Peter F Kador

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Aldose reductase (AR) is an enzyme responsible for converting glucose into sorbitol and galactose into galactitol. In the renal inner medulla, where sorbitol production plays a role in cellular osmoregulation, AR gene expression has been shown to be osmotically regulated. The present study examined the effects of the accumulation of the AR end product, galactitol, induced by galactose feeding, on AR gene expression and on the balance of other cellular osmolytes, including inositol, in the renal medulla. To differentiate between the effects of excess substrate, product, and intervening osmotic factors, rats were fed either control, galactose, galactose and sorbinil (and AR inhibitor), or control plus sorbinil diets. Renal papillae were assayed for AR mRNA, sodium, urea, galactose, galactitol, sorbitol, inositol, and other organic osmolytes. Galactose feeding resulted in a great accumulation of galactitol and reduction in AR mRNA levels in renal papillae. Associated with these changes was a significant depletion of renal papillary sorbitol, inositol, and glycerolphosphocholine. These effects were largely attenuated by sorbinil. The present findings suggest that renal cellular accumulation of the enzyme's polyol product causes downregulation of AR gene expression. Furthermore, our findings suggest that the inositol depletion associated with sorbitol or galactitol accumulation in various cell types during hyperglycemia may be a function of cellular osmoregulation.

Original languageEnglish (US)
Pages (from-to)1103-1108
Number of pages6
JournalJournal of Clinical Investigation
Volume86
Issue number4
DOIs
StatePublished - Jan 1 1990

Fingerprint

Galactitol
Aldehyde Reductase
Inositol
Galactose
Sorbitol
Kidney
Gene Expression
Messenger RNA
Enzymes
Osmoregulation
Hyperglycemia
Urea
Down-Regulation
Sodium
Diet
Glucose

Keywords

  • aldose reductase
  • galactitol
  • galactose
  • polyol
  • sorbitol

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Feedback inhibition of aldose reductase gene expression in rat renal medulla. Galactitol accumulation enzyme reduces mRNA levels and depletes cellular inositol content. / Bondy, C.; Cowley, B. D.; Lightman, S. L.; Kador, Peter F.

In: Journal of Clinical Investigation, Vol. 86, No. 4, 01.01.1990, p. 1103-1108.

Research output: Contribution to journalArticle

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