Coordinated Response of Aldose Reductase and Sorbitol Dehydrogenase Regulates Net Sorbitol Production in the Rat Renal Inner Medulla1

Sands, Jeff M.; Schrader, Dirk C.

doi:10.1159/000420669

Cited by 4 publications

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“…Aldose reductase, however, is primarily found in the inner medulla (Bondy et al, 1989). More work is needed to elucidate how these two enzymes can coordinate to regulate the level of sorbitol involved in the control of the osmotic pressure (Sands and Schrader, 1991).…”

Section: Discussionmentioning

confidence: 99%

Cloning, Sequencing, and Determination of the Sites of Expression of Mouse Sorbitol Dehydrogenase cDNA

Lee¹,

Lee²,

Lin³

et al. 1995

European Journal of Biochemistry

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Sorbitol dehydrogenase is one of the enzymes in the polyol pathway, which is thought to be implicated in the pathogenesis of diabetic complications. The cDNA encoding mouse sorbitol dehydrogenase was cloned from a liver library and its sequence was determined. The open reading frame encodes a product of 356 amino acids that shares high similarity with the human and rat liver sorbitol dehydrogenases (83% and 93% identity, respectively). The 3′‐untranslated region contains a truncated L1Md repeat element inserted in reverse relative to the sorbitol dehydrogenase cDNA. Northern‐blot hybridization showed that the testis has the highest level of expression, followed by kidney, liver, and lung. Low levels of expression were also observed in lens, brain, and skeletal muscle. In situ hybridization revealed that in the kidney, the highest concentration of sorbitol dehydrogenase mRNA is observed in the cortex, but is absent from the inner medulla. The parenchymal cells of the liver showed strong expression while the cells of the hepatic vasculature did not hybridize. The sorbitol dehydrogenase expression in the seminiferous tubules was mostly associated with the mature cells of the developing germ cells, confirming the usefulness of sorbitol dehydrogenase as an enzyme indicator for sexual maturation. The seminal vesicle, where most of the seminal fructose is produced, also showed a high level of expression in the epithelial cells. The mouse sorbitol dehydrogenase cDNA will be useful in the studies of the involvement of the polyol pathway in diabetic complications.

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Section: Discussionmentioning

confidence: 99%

Cloning, Sequencing, and Determination of the Sites of Expression of Mouse Sorbitol Dehydrogenase cDNA

Lee¹,

Lee²,

Lin³

et al. 1995

European Journal of Biochemistry

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Regulation of aldose reductase gene expression in renal cortex and medulla of rats

et al. 1995

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A role for aldose reductase-mediated production of polyol in the aetiology of diabetic nephropathy has been supported by both animal and clinical studies. In the renal medulla, the rate of polyol production is influenced in part by regulated changes in the level of aldose reductase gene expression. However, little is known about the expression of aldose reductase in the renal cortex. In this study, we evaluated the regulation of aldose reductase gene expression in the renal cortex and medulla in response to galactose feeding. Four groups of rats (n = 6) were treated for 9 weeks with control or galactose diet in the presence or absence of sorbinil, an aldose reductase inhibitor. In the renal medulla, galactose treatment produced a significant (p < 0.01) decrease in aldose reductase mRNA, to approximately 10% of control levels. Coadministration of sorbinil partially prevented the effect of galactose feeding on medullary aldose reductase mRNA (to 43% of control). Under basal conditions, the concentration of aldose reductase mRNA in the cortex was only 1% that of the renal medulla. Galactose feeding significantly reduced cortical aldose reductase mRNA by 29% relative to control (p < 0.01), and this was completely reversed by addition of sorbinil. Sorbinil administration to rats fed a control diet also decreased aldose reductase expression in the renal medulla and cortex. These results demonstrate that galactose feeding results in dynamic, polyol-dependent regulation of aldose reductase gene expression in the renal cortex as well as the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Cloning, Sequencing, and Determination of the Sites of Expression of Mouse Sorbitol Dehydrogenase cDNA

Lee¹,

Lee²,

Lin³

et al. 1995

Eur J Biochem

View full text Add to dashboard Cite

Sorbitol dehydrogenase is one of the enzymes in the polyol pathway, which is thought to be implicated in the pathogenesis of diabetic complications. The cDNA encoding mouse sorbitol dehydrogenase was cloned from a liver library and its sequence was determined. The open reading frame encodes a product of 356 amino acids that shares high similarity with the human and rat liver sorbitol dehydrogenases (83% and 93% identity, respectively). The 3'-untranslated region contains a truncated L1Md repeat element inserted in reverse relative to the sorbitol dehydrogenase cDNA. Northern-blot hybridization showed that the testis has the highest level of expression, followed by kidney, liver, and lung. Low levels of expression were also observed in lens, brain, and skeletal muscle. In situ hybridization revealed that in the kidney, the highest concentration of sorbitol dehydrogenase mRNA is observed in the cortex, but is absent from the inner medulla. The parenchymal cells of the liver showed strong expression while the cells of the hepatic vasculature did not hybridize. The sorbitol dehydrogenase expression in the seminiferous tubules was mostly associated with the mature cells of the developing germ cells, confirming the usefulness of sorbitol dehydrogenase as an enzyme indicator for sexual maturation. The seminal vesicle, where most of the seminal fructose is produced, also showed a high level of expression in the epithelial cells. The mouse sorbitol dehydrogenase cDNA will be useful in the studies of the involvement of the polyol pathway in diabetic complications.

show abstract

Coordinated Response of Aldose Reductase and Sorbitol Dehydrogenase Regulates Net Sorbitol Production in the Rat Renal Inner Medulla1

Cited by 4 publications

References 0 publications

Cloning, Sequencing, and Determination of the Sites of Expression of Mouse Sorbitol Dehydrogenase cDNA

Cloning, Sequencing, and Determination of the Sites of Expression of Mouse Sorbitol Dehydrogenase cDNA

Regulation of aldose reductase gene expression in renal cortex and medulla of rats

Cloning, Sequencing, and Determination of the Sites of Expression of Mouse Sorbitol Dehydrogenase cDNA

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