Abstract
In tests of osmotic tolerance of renal inner medullary cells in tissue culture, osmolality has usually been increased in a single step, whereas in vivo the increase occurs gradually over several hours. We previously found that more passage 2 mouse inner medullary epithelial (p2mIME) cells survive a linear increase in NaCl and urea from 640 to 1,640 mosmol/kgH2O over 20 h (which is similar to the change that may occur in vivo) than they do a step increase. The present studies examine accompanying differences in gene expression. Among mRNAs of genes known to be protective, tonicity-responsive enhancer binding protein and aldose reductase increase with a linear but decrease with a step increase; betaine transporter BGT1 decreases with a step but not a linear increase; heat shock protein 70.1 (HSP70.1) and HSP70.3 increase more with a linear than a step increase; and osmotic stress protein 94 and heme oxygenase-1 increase with a linear but decrease with a step increase. mRNAs for known urea-responsive proteins, GADD153 and Egr-1, increase with both a step and linear increase. A step increase in urea alone reduces mRNAs, similar to the combination of NaCl and urea, but a step increase in NaCl alone does not. HSP70 protein increases substantially with a linear rise in osmolality but does not change significantly with a step rise. We speculate that poorer survival of p2mIME cells with a step than with linear increase in NaCl and urea is accounted for, at least in part, by urea-induced suppression of protective genes, particularly HSP70.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / genetics
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Aldehyde Reductase / genetics
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Animals
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CCAAT-Enhancer-Binding Proteins / genetics
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Carrier Proteins / genetics
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Cells, Cultured
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DNA-Binding Proteins / genetics
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Early Growth Response Protein 1
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GABA Plasma Membrane Transport Proteins
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Gene Expression / drug effects
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Gene Expression / physiology
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HSP70 Heat-Shock Proteins / genetics*
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Heme Oxygenase (Decyclizing) / genetics
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Heme Oxygenase-1
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Hypoxanthine Phosphoribosyltransferase / genetics
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Immediate-Early Proteins*
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Kidney Medulla / cytology
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Kidney Medulla / physiology*
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Membrane Proteins / genetics
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Mice
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Myosin Type I / genetics
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Osmolar Concentration
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Osmotic Pressure
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RNA, Messenger / analysis
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Sodium Chloride / pharmacology
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Trans-Activators / genetics
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Transcription Factor CHOP
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Transcription Factors / genetics
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Urea / pharmacology
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Water-Electrolyte Balance / physiology*
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tau Proteins / genetics
Substances
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Actins
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CCAAT-Enhancer-Binding Proteins
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Carrier Proteins
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DNA-Binding Proteins
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Ddit3 protein, mouse
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Early Growth Response Protein 1
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Egr1 protein, mouse
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GABA Plasma Membrane Transport Proteins
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HERPUD1 protein, human
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HSP70 Heat-Shock Proteins
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HSPA4L protein, human
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Herpud1 protein, mouse
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Immediate-Early Proteins
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Membrane Proteins
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Nfat5 protein, mouse
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Osp94 protein, mouse
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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tau Proteins
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betaine plasma membrane transport proteins
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Transcription Factor CHOP
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Sodium Chloride
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Urea
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Aldehyde Reductase
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Heme Oxygenase (Decyclizing)
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Heme Oxygenase-1
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Hmox1 protein, mouse
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Hypoxanthine Phosphoribosyltransferase
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Myosin Type I