Characterization of Aldose Reductase from the Thick Ascending Limb of Henle’s Loop of Rabbit Kidney

Grunewald, R. Willi; Eckstein, Angela; Reisse, Claudius H.; Müller, Gerhard A.

doi:10.1159/000046047

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…Nevertheless, similar to results observed in our study, reduction of AR protein has been reported in mouse podocytes cultured in hyperosmolar HG medium for two weeks [35] and in arterial endothelium [36]. In turn, high glucose-induced loss of AR activity was found in epithelium from thick ascending limb of Henle's loop [37]. In our experiments, high glucose not only counteracted the activation of AR in HG-Hosm cells but also blunted the AR activity in HG-Nosm podocytes, despite upregulated enzyme protein (Figures 1, 4(a), and 4(c)).…”

Section: Discussionsupporting

confidence: 90%

Osmolarity and Glucose Differentially Regulate Aldose Reductase Activity in Cultured Mouse Podocytes

Lewko

Latawiec

Maryn

et al. 2011

Experimental Diabetes Research

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Podocyte injury is associated with progression of many renal diseases, including diabetic nephropathy. In this study we examined whether aldose reductase (AR), the enzyme implicated in diabetic complications in different tissues, is modulated by high glucose and osmolarity in podocyte cells. AR mRNA, protein expression, and activity were measured in mouse podocytes cultured in both normal and high glucose and osmolarity for 6 hours to 5 days. Hyperosmolarity acutely stimulated AR expression and activity, with subsequent increase of AR expression but decrease of activity. High glucose also elevated AR protein level; however, this was not accompanied by respective enzyme activation. Furthermore, high glucose appeared to counteract the osmolarity-dependent activation of AR. In conclusion, in podocytes AR is modulated by high glucose and increased osmolarity in a different manner. Posttranslational events may affect AR activity independent of enzyme protein amount. Activation of AR in podocytes may be implicated in diabetic podocytopathy.

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Section: Discussionsupporting

confidence: 90%

Osmolarity and Glucose Differentially Regulate Aldose Reductase Activity in Cultured Mouse Podocytes

Lewko

Latawiec

Maryn

et al. 2011

Experimental Diabetes Research

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“…BGT1 is present in the medullary thick ascending limbs of Henle loop and the medullary collecting ducts (Miyai et al, 1996; Zhou et al, 2012a). Aldose reductase (AR) is in the loop of Henle and inner medullary collecting ducts (Terubayashi et al, 1989; Schwartz et al, 1992; Grunewald et al, 2001). SMIT1 is predominantly present in the medullary and cortical thick ascending limb of Henle's loop and in the cells of the macula densa as well as to a lesser extent in the inner medullary collecting ducts (Yamauchi et al, 1995).…”

Section: Bgt1 and Betaine In Kidneymentioning

confidence: 99%

The betaine/GABA transporter and betaine: roles in brain, kidney, and liver

2014

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The physiological roles of the betaine/GABA transporter (BGT1; slc6a12) are still being debated. BGT1 is a member of the solute carrier family 6 (the neurotransmitter, sodium symporter transporter family) and mediates cellular uptake of betaine and GABA in a sodium- and chloride-dependent process. Most of the studies of BGT1 concern its function and regulation in the kidney medulla where its role is best understood. The conditions here are hostile due to hyperosmolarity and significant concentrations of NH4Cl and urea. To withstand the hyperosmolarity, cells trigger osmotic adaptation, involving concentration of a transcriptional factor TonEBP/NFAT5 in the nucleus, and accumulate betaine and other osmolytes. Data from renal cells in culture, primarily MDCK, revealed that transcriptional regulation of BGT1 by TonEBP/NFAT5 is relatively slow. To allow more acute control of the abundance of BGT1 protein in the plasma membrane, there is also post-translation regulation of BGT1 protein trafficking which is dependent on intracellular calcium and ATP. Further, betaine may be important in liver metabolism as a methyl donor. In fact, in the mouse the liver is the organ with the highest content of BGT1. Hepatocytes express high levels of both BGT1 and the only enzyme that can metabolize betaine, namely betaine:homocysteine –S-methyltransferase (BHMT1). The BHMT1 enzyme removes a methyl group from betaine and transfers it to homocysteine, a potential risk factor for cardiovascular disease. Finally, BGT1 has been proposed to play a role in controlling brain excitability and thereby represents a target for anticonvulsive drug development. The latter hypothesis is controversial due to very low expression levels of BGT1 relative to other GABA transporters in brain, and also the primary location of BGT1 at the surface of the brain in the leptomeninges. These issues are discussed in detail.

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“…The production of sorbitol via AR has consistently been documented as one of the more significant physiological functions in osmoadaptation in various parts of the kidney. Grunewald et al (2001) observed that AR played a role in osmoregulation throughout all portions of the kidney medulla, indicating a uniform dispersion of expression within the tissue. In dehydration and water conservation studies, NFAT5 and AR expression were increased in the kidneys of dehydrated rats and also in the kidneys of wood frogs during anoxia, when water conservation is essential for survival (Cha et al , 2001; Al-Attar et al.…”

Section: Discussionmentioning

confidence: 92%

NFAT5 is differentially expressed in Sprague-Dawley rat tissues in response to high salt and high fructose diets

et al. 2019

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Current diets contain an increasing amount of salt and high fructose corn syrup, but it remains unclear as to how dietary salt and fructose affect organ function at the molecular level. This study aimed to test the hypothesis that consumption of high salt and fructose diets would increase tissue-specific expression of two critical osmotically-regulated genes, nuclear factor of activated T-cells 5 ( NFAT5 ) and aldose reductase ( AR ). Fifty Sprague-Dawley rats were placed on a control, 4% NaCl, 8% NaCl, or 64% fructose diet for eight weeks. Fourteen different tissue samples were harvested and snap-frozen, followed by RNA purification, cDNA synthesis, and NFAT5 and AR gene expression quantification by real-time PCR.Our findings demonstrate that NFAT5 and AR expression are up-regulated in the kidney medulla, liver, brain, and adipose tissue following consumption of a high salt diet. NFAT5 expression is also up-regulated in the kidney cortex following consumption of a 64% fructose diet. These findings highlight the kidney medulla, liver, brain, and adipose tissue as being “salt-responsive” tissues and reveal that a high fructose diet can lead to enhanced NFAT5 expression in the kidney cortex. Further characterization of signaling mechanisms involved could help elucidate how these diets affect organ function long term.

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Characterization of Aldose Reductase from the Thick Ascending Limb of Henle’s Loop of Rabbit Kidney

Cited by 5 publications

References 33 publications

Osmolarity and Glucose Differentially Regulate Aldose Reductase Activity in Cultured Mouse Podocytes

Osmolarity and Glucose Differentially Regulate Aldose Reductase Activity in Cultured Mouse Podocytes

The betaine/GABA transporter and betaine: roles in brain, kidney, and liver

NFAT5 is differentially expressed in Sprague-Dawley rat tissues in response to high salt and high fructose diets

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