Disease relevance of Sord

• Sorbitol dehydrogenase overexpression potentiates glucose toxicity to cultured retinal pericytes [1].
• However, a functional role remains to be elucidated for SDH in the development and progression of diabetic retinopathy [1].
• The RT-PCR system developed in this study may be a useful tool in ascertaining the relative contributions of AR and SDH to the metabolic derangements resulting from the acceleration of polyol pathway activity in the target organ of diabetic complications [2].
• Sorbitol dehydrogenase activity was not detectable in lenses, among other tissues, making the pig a potential model for studies in experimental diabetes, particularly for the investigation of sorbitol dehydrogenase deficiency as a risk factor in the development of cataracts [3].
• However, it is unclear whether their action in diabetes mellitus depends directly on inhibiting the conversion of glucose to sorbitol by aldose reductase or indirectly by reducing the sorbitol available for subsequent metabolism to fructose by sorbitol dehydrogenase [4].

Psychiatry related information on Sord

• Finally, in Brattleboro rats, urine osmolality and levels of aldose reductase and taurine cotransporter mRNA increased in response to 1 day of water deprivation, whereas sorbitol dehydrogenase mRNA was unchanged [5].

High impact information on Sord

• Time course of serum enzyme elevations (alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase) indicated that actual infliction of liver injury by APAP peaked between 12 to 24 hours after the administration of APAP, whereas the ultimate outcome of that injury depended on the biological events thereafter [6].
• To analyze the effect of galactose, male Wistar rats were pretreated with lactulose (Duphalac, 9.1 gm per kg per day) and given Gal-N (375 mg per kg i.p.). After 24 hr, serum was analyzed for glutamic pyruvate transaminase, glutamate dehydrogenase, and sorbitol dehydrogenase activities [7].
• The VSMCs were found to express low levels of sorbitol dehydrogenase, and treatment with the sorbitol dehydrogenase inhibitor CP-166572 did not prevent high-glucose-induced PKC activation [8].
• These experiments were undertaken to assess the role of sorbitol dehydrogenase in mediating sorbitol pathway-linked neural and vascular dysfunction in rats with streptozocin-induced diabetes [9].
• Inhibition of sorbitol dehydrogenase. Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats [9].

Chemical compound and disease context of Sord

• Our present results suggest that SDH-mediated conversion of sorbitol to fructose and the resultant ROS generation may play an active role in the pathogenesis of diabetic retinopathy [1].
• In vitro addition of trichloroacetic acid, a metabolite of TCE to plasma, decreased the activities of SDH and ALT indicating that metabolites formed during TCE toxicity may interfere with plasma enzyme activities in vivo [10].
• Icariin significantly reduced the level of glutamic pyruvic transaminase and sorbitol dehydrogenase released resulting in a 76% protection from toxicity at concentration ranges from 1 microM to 20 microM [11].
• The extent of testicular toxicity was evident from the decreased activities of testicular marker enzymes (sorbitol dehydrogenase and glucose-6-phosphate dehydrogenase) [12].
• 1. Subchronic treatment of male and female rats with CCl4 (0.2 ml/kg orally twice weekly) and drinking water containing 5% ethanol for four weeks led to a 20 to 40-fold increase in serum sorbitol dehydrogenase activity and to an augmentation of the liver triglyceride and hydroxyproline contents, indicating steatosis and fibrosis, respectively [13].

Biological context of Sord

• Analysis of gene expression of aldose reductase and sorbitol dehydrogenase in rat Schwann cells by competitive RT-PCR method using non-homologous DNA standards [2].
• Two separate cDNA-clones, together coding for rat sorbitol dehydrogenase, have been isolated from a liver cDNA library in lambda gt11 by screening with oligonucleotide probes [14].
• Osmoregulation of aldose reductase and sorbitol dehydrogenase in cultivated interstitial cells of rat renal inner medulla [15].
• The full-length cDNA insert contained 2277 base pairs (bp), starting 182 bp upstream from an ATG codon where translation to the active enzyme SDH is presumed to be initiated [16].
• The sequence data indicate that the nucleotide environment around this ATG codon is more favorable towards it being the actual open reading frame (ORF) for a pre-SDH than the ATG codon preceding the nucleotide sequence for SDH [16].

Anatomical context of Sord

• A cDNA clone encoding rat sorbitol dehydrogenase (SDH) was isolated from a rat testis lambda ZAP II cDNA library [16].
• Localization and physiological implication of aldose reductase and sorbitol dehydrogenase in reproductive tracts and spermatozoa of male rats [17].
• The activities and protein levels of AR and SDH were higher in the ovary than in the oviduct and uterus [18].
• However, in testis, the cells that express these 2 enzymes differed; whereas AR was expressed in Sertoli cells and to lesser extent in spermatogenic cells, SDH was detected in spermatogenic cells of seminiferous tubules [17].
• SDH protein levels were higher during spermatid elongation, and large amounts of SDH were carried over to the spermatozoa [17].

Associations of Sord with chemical compounds

• SDH overexpression was found to significantly stimulate ROS generation in high glucose-exposed pericytes and subsequently potentiate the cytopathic effects of glucose [1].
• Fidarestat, a newly developed AR inhibitor, and N-acetylcysteine, an antioxidant, completely prevented these deleterious effects of SDH overexpression on pericytes [1].
• Nonradioactive in situ hybridization studies on sections from formalin-fixed and paraffin-embedded, normally concentrating kidneys showed strong expression of BGT, SMIT, and AR mRNAs in interstitial and collecting duct cells of the papilla, whereas expression of SDH mRNA was much weaker in both cell types [19].
• Swelling and liquefaction of lens fibers were observed in the subcapsular and supranuclear region of 60 week old OLETF rats, as well as decreased lenticular sorbitol, and markedly increased SDH activity compared with rats at 40 weeks [20].
• This variance occurs at position 957-960, where threonine is coded for instead of aspartic acid; in the rat testis SDH cDNA, we find the sequence is ACG instead of GAC, as was reported for the rat liver SDH cDNA [16].

Physical interactions of Sord

• Lactate dehydrogenase isozyme C4 (LDH-C4) and sorbitol dehydrogenase (SDH) were used as germ cell markers and leucine aminotransferase (LAT) and androgen binding protein (ABP) were used as Sertoli cell markers [21].

Other interactions of Sord

• This study demonstrates AR and SDH in substructures of the kidney [22].
• SDH mRNA was most abundant in testes and liver, but was absent from lens [23].
• Sorbitol dehydrogenase: cDNA coding for the rat enzyme. Variations within the alcohol dehydrogenase family independent of quaternary structure and metal content [14].
• A portion of the glucose was found to be channelled from the normal glycolytic route to polyol pathway, evident by the reduced hexokinase activity and increased polyol pathway enzymes aldose reductase and sorbitol dehydrogenase activity causing accumulation of sorbitol and fructose in diabetic conditions [24].
• 3. Spermatozoa, unlike epididymal tissue, contained sorbitol dehydrogenase but lacked ATP citrate lyase [25].

Analytical, diagnostic and therapeutic context of Sord

• Northern-blot hybridization analysis showed that SDH mRNA is a doublet, one band of 4 kb and the other of 2.3-2.4 kb, in both the rat liver and the rat lens, further confirming that the isolated SDH cDNA constituted a full-length cDNA [16].
• The enzymatic activities, expression, and localization of AR and SDH were studied in reproductive tracts and spermatozoa of male rats by immunohistochemistry, Western blotting, and enzyme assays [17].
• To identify the polyol pathway step most relevant to complications, particularly neuropathy, we compared the biochemical effects of a sorbitol dehydrogenase inhibitor, WAY-135706, (250 mg.kg-1.day-1) and an ARI, WAY-121509, (10 mg.kg-1.day-1) on a variety of tissues, and their effects on nerve perfusion and conduction velocity [4].
• Second, in rats fed a low-protein diet for 3 wk, aldose reductase mRNA increased two-fold, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged [5].
• Creatine kinase release during reperfusion, a marker of myocardial ischemic injury, was markedly attenuated in SDH-inhibited hearts [26].

References