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Nephrol Dial Transplant (2003) 18: 2255-2261
© 2003 European Renal Association-European Dialysis and Transplant Association


Original Article

Osmoregulation of aldose reductase and sorbitol dehydrogenase in cultivated interstitial cells of rat renal inner medulla

Jürgen Steffgen1,*, Katrin Kampfer1, Clemens Grupp1, Christoph Langenberg1, Gerhard A. Müller1 and R. Willi Grunewald1

1Abteilung Nephrologie und Rheumatologie, Georg-August-Universität Göttingen, Göttingen, Germany

Correspondence and offprint requests to: Dr Jürgen Steffgen, Abteilung Klinische Forschung, Boehringer-Ingelheim Pharma GmBH & Co KG, D-88397 Biberach an der Riss, Germany. Email: jsteffgen{at}gmx.de.

Background. Little is known about sorbitol metabolism in renal papillary interstitial cells. For characterization we studied regulation of sorbitol synthesis by aldose reductase (AR) and degradation by sorbitol dehydrogenase (SDH) in papillary interstitial cells.

Methods. Interstitial cells were isolated from rat renal inner medulla to a pure cell fraction. mRNA was isolated from cultivated cells and sorbitol, AR and SDH activity were determined enzymatically in homogenates.

Results. Sorbitol concentration in these cells at 300 mosmol/l was 4.4±0.3 vs 78±3.6 µmol/g protein at 600 mosmol/l. At steady-state conditions at 300 mosmol/l, AR activity was nearly the same as SDH activity (15.1±1.6 vs 16.6±2.0 U/g protein). At 600 mosmol/l, AR activity increased to 82.5±11.4 U/g protein and SDH activity to 31.5±6.0 U/g protein. Studying the time course of enzyme activity after changing osmolarity from 300 to 600 mosmol/l, we found half maximal stimulation after 2–3 (AR) or 3 (SDH) days. The amount of AR-mRNA preceded the rise of enzyme activity, whereas SDH-mRNA was not significantly influenced. Lowering osmolarity from 600 to 300 mosmol/l, enzyme activity decreased to less than half within 2 (AR) or 1 (SDH) day(s).

Conclusions. The results suggest that sorbitol metabolism contributes to handling of osmotic stress in rat renal papillary interstitial cells.

Keywords: aldose reductase; enzyme activity; osmoregulation; sorbitol; sorbitol dehydrogenase

*Present address: Abteilung Klinische Forschung, Boehringer-Ingelheim Pharma GmBH & Co KG, Biberach an der Riss, Germany


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