Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renal response to changes in hydration includes variation in intracellular sorbitol, a major inner medullary osmolyte. To examine the mechanism for changes in net sorbitol production, we measured activities of enzymes regulating sorbitol production (aldose reductase) and degradation (sorbitol dehydrogenase) in untreated, water diuretic, and antidiuretic (water restriction and/or vasopressin administration) rats. Collecting duct segments dissected from collagenase-treated kidneys of Sprague-Dawley rats were divided into outer medullary and three distinct inner medullary regions. Aldose reductase activity increased during antidiuresis and decreased during diuresis. In contrast, sorbitol dehydrogenase activity was very low during antidiuresis and increased during diuresis. These changes in enzyme activity were found after 3 days, but not after 1 day, of water diuresis/antidiuresis. Enzyme activity changed only in the deepest 50% of the inner medullary collecting duct. Thus, there is coordinated regulation of aldose reductase and sorbitol dehydrogenase activities so that (a) during water diuresis, aldose reductase activity decreases while sorbitol dehydrogenase activity increases; and (b) during antidiuresis (water restriction and/or vasopressin administration), aldose reductase activity increases while sorbitol dehydrogenase activity remains low. We conclude that long-term osmoregulation in response to physiologic stimuli involves both aldose reductase and sorbitol dehydrogenase activities in rat terminal inner medullary collecting duct segments.
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PMID:Coordinated response of renal medullary enzymes regulating net sorbitol production in diuresis and antidiuresis. 212 8

Sorbitol participates in the osmoregulation of several renal cells and has also been found in isolated inner medullary collecting duct (IMCD) cells in primary culture. Therefore, osmotic regulation and distribution of sorbitol and the key enzymes of sorbitol metabolism, aldose reductase and sorbitol dehydrogenase in the renal inner medulla, were investigated in vivo under various osmotic conditions (control, diuresis, antidiuresis). In homogenates of the renal inner medulla of Wistar rats, the sorbitol content correlated with the urine osmolarity [68 +/- 12 mumol/g protein (control), 28 +/- 9 mumol/g (diuresis), 110 +/- 15 mumol/g (antidiuresis)]. Similar results were obtained for the activity of aldose reductase (sorbitol synthesis) [25 +/- 4 U/g (control), 19 +/- 3 U/g (diuresis), and 48 +/- 7 U/g (antidiuresis)]. On the contrary, the activity of sorbitol dehydrogenase (sorbitol degradation) was significantly increased to 1.26 +/- 0.42 U/g under diuretic conditions vs. control (0.84 +/- 0.14 U/g, P < 0.05). These results demonstrate the correlation between the enzymes of sorbitol synthesis and sorbitol degradation in the intact inner medulla and the urine osmolarity in vivo. Whereas the aldose reductase activity was 2.3-fold enriched in IMCD cells, the specific activity of sorbitol dehydrogenase was relatively increased in a preparation of enriched interstitial cells. This distribution was not dependent on the various diuretic conditions. These results indicate that enzymes of synthesis and of degradation of sorbitol are osmotically regulated in vivo. Therefore, the enzymatic activities of sorbitol synthesis appear to be primarily located in epithelial cells, whereas enzymatic activities of sorbitol degradation seem to be localized in interstitial cells of the renal inner medulla.
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PMID:Renal inner medullary sorbitol metabolism. 750 36

Sorbitol plays an important role in the osmoregulation of several renal cell types, especially the inner medullary collecting duct (IMCD) cells. Very little information is available concerning the expression of the enzymes of sorbitol metabolism (aldose reductase (AR) and sorbitol dehydrogenase (SDH)) on the RNA level under different osmotic conditions. We employed a RT-PCR-based strategy to investigate the regulation of mRNA coding for AR and SDH. For AR two primers (derived from the sequence of the rat eye lens) were chosen which amplify a 668-bp product. For SDH (considering the sequence of rat liver) three primers were chosen, amplifying a 367- and a 1, 068-bp fragment. Digestion with restriction enzymes and sequencing of the products clearly indicate that the specific mRNA of AR and SDH was amplified. By relative quantitative determination of the amplification products a more than 4-fold increase in mRNA for AR in IMCD cells was observed within 24 h after increasing the extracellular osmolarity from 600 to 900 mosm/l. Decreasing the osmolarity from 600 to 300 mosm/l resulted in a reduction in the mRNA level by 70%. The complete adaptation of the AR activity needed 3 (increasing osmolarity) and 6 days (decreasing osmolarity). Osmotically induced alterations in the levels of mRNA coding for SDH could not be observed. These results suggest that the adaptation of sorbitol synthesis occurs by a rapid regulation of transcription or stability of specific mRNA. For a complete synthesis or degradation of AR 3-6 days are necessary. Thus sorbitol synthesis in IMCD is more rapidly adapted to increasing osmolarities than to decreasing osmolarities.
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PMID:Rat renal expression of mRNA coding for aldose reductase and sorbitol dehydrogenase and its osmotic regulation in inner medullary collecting duct cells. 994 55

Sorbitol plays a major role in the maintenance of cell volume and functional integrity of several renal cells. Sorbitol synthesis takes place in inner collecting duct cells, whereas sorbitol dehydrogenase activity, which catalyzes the degradation of sorbitol to fructose, could mainly be detected in renal inner medullary interstitial cells. Therefore, we supposed that interstitial cells would require a sorbitol transport into the cells. However, such a transport system has not yet been described. Therefore, we have characterized the uptake of sorbitol in immortalized interstitial TK-173 cells, which were derived from human renal fibroblasts. Comparable to fresh isolated renal fibroblasts of the rat, immortalized TK-173 cells have a high sorbitol dehydrogenase activity. In this report, a temperature-dependent sorbitol uptake with saturation kinetics could be detected in immortalized TK-173 cells. The transport is characterized by a high velocity (Vmax 84 mmol/l x h) and an apparent Km of 10 mmol/l. The sorbitol uptake is independent of membrane potential, sodium, and chloride. Altogether, the physiological characteristics of this sorbitol transport are different from those of the osmotically regulated sorbitol efflux from epithelial cells. These results provide evidence that TK-173 cells derived from renal fibroblasts have a specific sorbitol transport. Furthermore, these data suggest a cooperation between epithelial and interstitial cells concerning osmoregulation.
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PMID:Evidence for a sorbitol transport system in immortalized human renal interstitial cells. 1170

Sorbitol plays an important role in the osmotic regulation of the mammalian kidney. Sorbitol synthesis is regulated by the enzyme aldose reductase (AR) and its degradation to fructose is catalyzed by the enzyme sorbitol dehydrogenase (SDH). Various data exist on the polyol pathway on the rat kidney, but little is known about the distribution of the polyol pathway enzymes in the human kidney. Determination of enzyme activities and a semiquantitative determination of mRNA expression, immunohistochemistry and in-situ hybridisation in healthy human kidney tissue was carried out. The enzyme activity of AR showed a fourfold increase from cortex to papilla, while SDH-activity dropped from cortex to papilla by a factor of four. Corresponding data was obtained at the mRNA level from the semiquantitative polymerase chain reaction (PCR). Additional differentiation at the cellular level reveals both enzymes in cells of the proximal and distal tubules, thick ascending loop, thin loop and collecting duct. Studies of enzyme activity and expression by immunohistochemistry, PCR and in-situ hybridization presented corresponding results with respect to the localization of the enzymes, which match the experimental data obtained from rats very well. Thus, the established rat model might well represent the situation in the human kidney, too.
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PMID:Localization of the polyol pathway in the human kidney. 1922 47

Affymetrix GeneChip technology was employed to detect differentially expressed genes in inner medullary collecting duct (IMCD3) cells grown under isotonic and hypertonic conditions. A marked up-regulation was found for the zinc-finger protein ZAC1 under hypertonic stress (219-fold, p < 0.001). Changes in expression for ZAC1 were verified by quantitative PCR for message and Western blotting for protein. In mouse and human kidney tissues, ZAC1 expression was substantial in the papilla and was absent in the cortex. Furthermore, ZAC1 expression significantly increased in the papilla of mice following 36 h of fluid restriction and decreased in polyuric mice consuming sucrose in water. Because ZAC1 has been described to be a potential negative regulator of sorbitol dehydrogenase (SDH) in hippocampal cells, we examined whether this relationship also occurs in kidney cells under hypertonic stress. We found that stable IMCD3 clones silenced for ZAC1 to varying levels demonstrated an inverse effect on SDH expression. ZAC1 binds to a consensus repression site within the promoter of SDH, pointing to a mechanism whereby ZAC1 acts by repressing SDH transcriptional activity during hypertonic conditions. Taken together, these data strongly suggest that ZAC1 is up-regulated under hypertonic stress and negatively regulates expression of SDH, allowing for accumulation of sorbitol as a compatible organic osmolyte.
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PMID:ZAC1 is up-regulated by hypertonicity and decreases sorbitol dehydrogenase expression, allowing accumulation of sorbitol in kidney cells. 1942 11