Chronic hyperosmolarity mediates constitutive expression of molecular chaperones and resistance to injury.
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.
Santos
Bento C
BC
Department of Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston 02115, USA.
Pullman
James M
JM
Chevaile
Alejandro
A
Welch
William J
WJ
Gullans
Steven R
SR
D000223:Adaptation, Psychological / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007679:Kidney Medulla / Q000166:cytology / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018832:Molecular Chaperones / Q000096:biosynthesis*; D009994:Osmolar Concentration; D016877:Oxidants / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D014508:Urea / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D003470:Culture Media; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D016877:Oxidants; D012333:RNA, Messenger; D012965:Sodium Chloride; D014508:Urea; D020928:Mitogen-Activated Protein Kinases; D019256:Cadmium Chloride