Abstract
Upon hypertonic stress most often resulting from high salinity, cells need to balance their osmotic pressure by accumulating neutral osmolytes called compatible osmolytes like betaine, myo-inositol, and taurine. However, the massive uptake of compatible osmolytes is a slow process compared with other defense mechanisms related to oxidative or heat stress. This is especially critical for cycling cells as they have to double their volume while keeping a hospitable intracellular environment for the molecular machineries. Here we propose that clustered cells can accelerate the supply of compatible osmolytes to cycling cells via the transit, mediated by gap junctions, of compatible osmolytes from arrested to cycling cells. Both experimental results in epithelial normal rat kidney cells and theoretical estimations show that gap junctions indeed play a key role in cell adaptation to chronic hypertonicity. These results can provide basis for a better understanding of the functions of gap junctions in osmoregulation not only for the kidney but also for many other epithelia. In addition to this, we suggest that cancer cells that do not communicate via gap junctions poorly cope with hypertonic environments thus explaining the rare occurrence of cancer coming from the kidney medulla.
MeSH terms
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Adaptation, Physiological / drug effects
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Adaptation, Physiological / physiology*
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Animals
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Betaine / metabolism
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Betaine / pharmacology
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Cell Communication / physiology
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Cell Count
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Cell Line
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Cell Proliferation / drug effects
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Connexin 43 / genetics
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Connexin 43 / metabolism
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Cytoskeleton / metabolism
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Cytoskeleton / pathology
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / pathology
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Epithelial Cells / physiology*
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Gap Junctions / drug effects
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Gap Junctions / pathology
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Gap Junctions / physiology*
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Glycyrrhetinic Acid / pharmacology
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HeLa Cells
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Humans
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Hypertonic Solutions
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Inositol / metabolism
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Inositol / pharmacology
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Kidney / cytology
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Kidney / physiology*
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Microtubules / drug effects
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Microtubules / metabolism
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Microtubules / pathology
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Nocodazole / pharmacology
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Oleic Acids / pharmacology
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RNA, Small Interfering / genetics
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Rats
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Saline Solution, Hypertonic
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Stress Fibers / metabolism
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Stress Fibers / pathology
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Stress, Physiological / drug effects
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Stress, Physiological / physiology*
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Water-Electrolyte Balance / drug effects
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Water-Electrolyte Balance / physiology*
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Wound Healing / drug effects
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Wound Healing / physiology
Substances
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Connexin 43
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Hypertonic Solutions
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Oleic Acids
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RNA, Small Interfering
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Saline Solution, Hypertonic
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Betaine
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Inositol
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oleylamide
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Glycyrrhetinic Acid
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Nocodazole