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  • 1
    Electronic Resource
    Electronic Resource
    Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1 (2000)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 408 (2000), S. 211-216 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Cytokines are multifunctional mediators that classically modulate immune activity by receptor-mediated pathways. Macrophage migration inhibitory factor (MIF) is a cytokine that has a critical role in several inflammatory conditions but that also has endocrine and enzymatic functions. The ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/35041591
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibition of NaCl-induced heat shock protein 72 expression renders MDCK cells susceptible to high urea concentrations (1999)
    Springer
    Pflügers Archiv 437 (1999), S. 611-616 
    Details
    ISSN: 1432-2013
    Keywords: Key words Antisense ; Heat shock proteins ; Hypertonic stress ; MDCK cells ; Transfection ; Urea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Exposure of Madin-Darby canine kidney (MDCK) cells to elevated extracellular NaCl concentrations is associated with increased heat shock protein 72 (HSP72) expression and improved survival of these pretreated cells upon exposure to an additional 600 mM urea in the medium. To establish a causal relationship between HSP72 expression and cell protection against high urea concentrations, two approaches to inhibit NaCl-induced HSP72 synthesis prior to exposure to 600 mM urea were employed. First, the highly specific p38 kinase inhibitor SB203580 was added (100 µM) to the hypertonic medium (600 mosm/kg H2O by NaCl addition, 2 days of exposure), which significantly reduced HSP72 mRNA abundance and HSP72 content. Survival of these cells after a 24-h urea treatment (600 mM) was markedly curtailed compared with appropriate controls. Second, a pcDNA3-based construct, containing 322 bases of the HSP72 open reading frame in antisense orientation and the geneticine resistance gene, was transfected into MDCK cells. Clones with strong inhibition of HSP72 synthesis and others which express the protein at normal levels (comparable to nontransfected MDCK cells) after heat shock treatment or hypertonic stress were established. When these transformants were subjected to hypertonic stress for 2 days prior to exposure to an additional 600 mM urea for 24 h, cell survival was significantly reduced in those clones in which HSP72 expression was strongly inhibited. These results provide further evidence for the protective function of HSP72 against high urea concentrations in renal epithelial cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050824
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  • 3
    Electronic Resource
    Electronic Resource
    Expression of aldose reductase, sorbitol dehydrogenase and Na+/myo-inositol and Na+/Cl–/betaine transporter mRNAs in individual cells of the kidney during changes in the diuretic state (1999)
    Springer
    Pflügers Archiv 437 (1999), S. 248-254 
    Details
    ISSN: 1432-2013
    Keywords: Key words Aldose reductase (AR) ; Antidiuresis ; Diuresis ; Na+/Cl-/betaine cotransporter (BGT) ; Na+/myo-inositol cotransporter (SMIT) ; Non-radioactive in situ hybridization ; Osmoregulation ; Sorbitol dehydrogenase (SDH)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of changes in medullary extracellular tonicity on mRNA expression for aldose reductase (AR), sorbitol dehydrogenase (SDH), Na+/Cl–/betaine (BGT) and Na+/myo-inositol (SMIT) cotransporter in different kidney zones was studied using Northern blot analysis and non-radioactive in situ hybridization in four groups of rats: controls, acute diuresis (the loop diuretic furosemide was administered), chronic diuresis (5 days of diuresis), and antidiuresis [5 days of diuresis followed by 24 h deamino-Cys1,d-Arg8 vasopressin (dDAVP)]. Acute administration of the loop diuretic furosemide significantly reduced AR, SMIT and BGT gene expression in the inner and outer medulla compared with controls. Administration of dDAVP to chronically diuretic rats raised the expression of these three mRNAs in the inner but not the outer medulla compared with the chronically diuretic rats. None of these alterations in medullary tonicity significantly changed SDH expression. The in situ hybridization studies showed AR, BGT and SMIT mRNAs to be expressed in both epithelial and non-epithelial cells of the outer and inner medulla. The various cell types (epithelial, endothelial and interstitial cells) differed in their expression pattern and intensity of AR, SDH, BGT and SMIT mRNA, but the inner medullary cells responded uniformly to a decrease in extracellular tonicity with a reduction, and to an increase with enhancement of their AR, BGT and SMIT expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050776
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  • 4
    Electronic Resource
    Electronic Resource
    Expression of Na+/Cl–/betaine and Na+/myo-inositol transporters, aldose reductase and sorbitol dehydrogenase in macula densa cells of the kidney (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 807-809 
    Details
    ISSN: 1432-2013
    Keywords: Key words Aldose reductase ; In situ hybridization ; Macula densa ; Na+/Cl ; /betaine cotransporter ; Na+/myo-inositol cotransporter ; Osmolytes ; Sorbitol dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has been suggested that macula densa cells may be exposed to hyperosmotic stress. Since chronic exposure to hypertonic stress causes the amount of intracellular organic osmolytes to increase, the expression of transporters and enzymes that participate in the intracellular accumulation of organic osmolytes was examined using non-radioactive in situ hybridization in the macula densa region of control rats and furosemide-treated animals. Both the sodium- and chloride-dependent betaine transporter (BGT) and sodium-dependent myo-inositol transporter (SMIT) were expressed preferentially in macula densa cells and for both mRNAs the signal intensity was visibly reduced by furosemide. The enzymes aldose reductase (which mediates the conversion of glucose to sorbitol) and sorbitol dehydrogenase (which converts sorbitol into fructose) were expressed not only in macula densa cells but also in the surrounding tubular cells, and the expression was insensitive to furosemide. Thus it remains unclear whether the expression of BGT and SMIT is related to a putative hypertonic juxtaglomerular region.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050707
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  • 5
    Electronic Resource
    Electronic Resource
    Cellular response to osmotic stress in the renal medulla (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 814-827 
    Details
    ISSN: 1432-2013
    Keywords: Key words Antidiuresis ; Diuresis ; Heat shock proteins ; Ionic strength ; Organic osmolytes ; Osmotic stress ; Renal medulla
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cells of the renal medulla, which are exposed under normal physiological conditions to widely fluctuating extracellular solute concentrations, respond to hypertonic stress by accumulating the organic osmolytes glycerophosphorylcholine (GPC), betaine, myo-inositol, sorbitol and free amino acids. Increased intracellular contents of these osmolytes are achieved by a combination of increased uptake (myo-inositol and betaine) and synthesis (sorbitol, possibly GPC), decreased degradation (GPC) and reduced osmolyte release. In the medulla of the concentrating kidney, accumulation of organic osmolytes, which do not perturb cell function even at high concentrations, allows the maintenance of ”normal” intracellular concentrations of inorganic electrolytes. Adaptation to decreasing extracellular solute concentrations, e.g. diuresis, is achieved primarily by activation of pathways allowing the efflux of organic osmolytes, and secondarily by inactivation of production (sorbitol) and uptake (betaine, myo-inositol) and stimulation of degradation (GPC). Apart from modulation of the osmolyte content, osmolality-dependent reorganization of the cytoskeleton and expression of specific stress proteins (heat shock proteins) may be further, as yet poorly characterized, components of the regulatory systems involved in the adaptation of medullary cells to osmotic stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050710
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of long-term changes in medullary osmolality on heat shock proteins HSp25, hsp60, HSP72 and HSP73 in the rat kidney (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 705-712 
    Details
    ISSN: 1432-2013
    Keywords: Key words Diuresis/antidiuresis ; Osmotic stress ; HSP25 ; HSP60 ; HSP72 ; HSP73 ; Transcription ; Translation ; Medullary hypertonicity ; Phosphorylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The influence of diuresis and antidiuresis on the expression of heat shock proteins (HSP) 25, 60, 72 and 73 in the renal cortex and outer and inner medulla of Wistar rats was analysed. Medullary osmolality was reduced by long-term diuresis (3% sucrose in the drinking water for 3 weeks) and subsequently enhanced by transition to a concentrating state by giving normal drinking water again in combination with deamino-D-arginine vasopressin (dDAVP) for 5 days. Western blot analyses revealed that neither HSP73 nor HSP60 was influenced by any treatment. The HSP72 level in the medulla was markedly reduced (50%) when osmolality was lowered and increased when tonicity was high. RNAse protection assays showed that the effects on HSP72 are parallelled in general by changes in HSP72 mRNA. While levels of HSP25 were not influenced, isoelectric focusing revealed that the degree of phosphorylation of outer and inner medullary HSP25 increased following both treatments. It thus seems that HSP73 and HSP60 are not directly involved in the long-term adaptation to varying medullary osmolalities. The correlation between changes in osmolality and amounts of the major stress-inducible HSP72 in the medulla implies that medullary hypertonicity is stressful for kidney cells. Furthermore, adaptation to pronounced changes in the osmolality of the environment most likely involves phosphorylation of HSP25.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050572
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  • 7
    Electronic Resource
    Electronic Resource
    Pretreatment with hypertonic NaCl protects MDCK cells against high urea concentrations (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 407-414 
    Details
    ISSN: 1432-2013
    Keywords: Key words MDCK cells ; Hypertonic stress ; NaCl ; Urea ; Organic osmolytes ; Heat shock proteins ; Cell viability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In antidiuresis, the cells of the renal medulla are exposed to high extracellular concentrations of NaCl and urea. Since urea equilibrates with the intracellular compartment and is known to perturb intracellular macromolecules, high urea concentrations may well disturb the structure and function of cell proteins. Two types of organic substances are believed to counteract the adverse effects of high intracellular urea concentrations: specific organic osmolytes of the trimethylamine family [betaine and glycerophosphorylcholine (GPC)], which accumulate in renal medullary cells during prolonged periods of antidiuresis and cytoprotective heat shock proteins (HSPs), the tissue content of two of which (HSPs 27 and 72) is much higher in the inner medulla than in the iso-osmotic renal cortex. To evaluate the contribution of trimethylamines and HSPs to cytoprotection in the presence of high urea concentrations, the effect of HSP induction and osmolyte accumulation prior to exposure to high urea concentrations was examined in Madin-Darby canine kidney (MDCK) cells. Accumulation of organic osmolytes and synthesis of HSP27 and HSP72 was initiated by hypertonic stress (increasing the osmolality of the medium from 290 to 600 mosmol/kg H2O by NaCl addition). Control, non-conditioned cells remained in the isotonic medium for the same period. Upon subsequent exposure to an additional 600 mM urea in the medium for 24 h, 90% of the osmotically conditioned cells but only 15% of non-conditioned cells survived. The HSP72 and trimethylamine contents of the NaCl-conditioned MDCK cells, but not HSP27 content, correlated positively with cell survival. To separate the effects of organic osmolytes and HSP72, chronically NaCl-adapted MDCK cells were returned to isotonic medium for 1 or 2 days, so depleting them of trimethylamine osmolytes. HSP72, with its longer half life, remained elevated. Subsequent exposure of these cells to 600 mM urea in the medium resulted in about 80% survival. These results suggest that in MDCK cells and probably in the renal medulla, HSP72 and perhaps additional protective factors contribute substantially to the resistance against high urea concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050531
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