Chronic hyperosmolarity mediates constitutive expression of molecular chaperones and resistance to injury

Am J Physiol Renal Physiol. 2003 Mar;284(3):F564-74. doi: 10.1152/ajprenal.00058.2002. Epub 2002 Oct 29.


Renal medullary cells are exposed to elevated and variable osmolarities and low oxygen tension. Despite the harsh environment, these cells are resistant to the effects of many harmful events. To test the hypothesis that this resistance is a consequence of these cells developing a stress tolerance phenotype to survive in this milieu, we created osmotically tolerant cells [hypertonic (HT) cells] by gradually adapting murine inner medullary collecting duct 3 cells to hyperosmotic medium containing NaCl and urea. HT cells have a reduced DNA synthesis rate, with the majority of cells arrested in the G(0)/G(1) phase of the cell cycle, and show constitutive expression of heat shock protein 70 that is proportional to the degree of hyperosmolarity. Unlike acute hyperosmolarity, chronic hyperosmolarity failed to activate MAPKs. Moreover, HT cells acquired protein translational tolerance to further stress treatment, suggesting that HT cells have an osmotolerant phenotype that is analogous to thermotolerance but is a permanent condition. In addition to osmotic shock, HT cells were more resistant to heat, H(2)O(2), cyclosporin, and apoptotic inducers, compared with isotonic murine inner medullary duct 3 cells, but less resistant to amphotericin B and cadmium. HT cells demonstrate that in renal medullary cells, hyperosmotic stress activates biological processes that confer cross-tolerance to other stressful conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Psychological / drug effects
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Cadmium Chloride / pharmacology
  • Cell Division / drug effects
  • Cell Line
  • Culture Media / pharmacology
  • Electrophoresis, Gel, Two-Dimensional
  • Flow Cytometry
  • HSP70 Heat-Shock Proteins / analysis
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Kidney Medulla / cytology
  • Kidney Medulla / metabolism*
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Chaperones / biosynthesis*
  • Osmolar Concentration
  • Oxidants / pharmacology
  • RNA, Messenger / metabolism
  • Sodium Chloride / pharmacology
  • Stress, Physiological / metabolism*
  • Subcellular Fractions / chemistry
  • Subcellular Fractions / metabolism
  • Urea / pharmacology


  • Anti-Bacterial Agents
  • Culture Media
  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones
  • Oxidants
  • RNA, Messenger
  • Sodium Chloride
  • Urea
  • Mitogen-Activated Protein Kinases
  • Cadmium Chloride