Document Detail

Response of renal inner medullary epithelial cells to osmotic stress.
MedLine Citation:
PMID:  12443923     Owner:  NLM     Status:  MEDLINE    
As part of the urinary concentrating mechanism, renal inner medullary epithelial (IME) cells are normally exposed to variable and often very high interstitial levels of NaCl and urea, yet they survive and function. We have been studying the mechanisms involved, using an established cell line (mIMCD3). Acute increase of NaCl or urea from 300 to >500 mOsmol/kg causes cell cycle delay and apoptosis. High NaCl, but not high urea, causes DNA double strand breaks. At 500-600 mOsmol/kg inhibition of DNA replication following high NaCl depends on activation of the tumor suppressor protein, p53, and provides time for DNA repair. If p53 expression is suppressed, cells continue to replicate DNA, and many of those cells die. At higher levels of NaCl (>650 mOsmol/kg) the mitochondria rapidly depolarize and most cells die within a few hours despite a high level of p53 protein (which, however, is less phosphorylated than at 500 mOsmol/kg). Since the levels of NaCl and urea that kill mIMCD3 cells are much lower than those that exist in vivo, we investigated the difference, using early passage mouse IME cells under various conditions. Passage 2 IME cells survive higher levels of NaCl and urea than do mIMCD3 cells, but still not levels as high as in vivo. However, when the osmolality is increased linearly over 20 h, as occurs in vivo, rather than as a single step, cell survival increases to levels close to those found in vivo. We conclude that a more gradual increase in osmolality provides time for accumulation of organic osmolytes and activation of heat shock protein, previously known to be important for cell survival.
Maurice B Burg
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Comparative biochemistry and physiology. Part A, Molecular & integrative physiology     Volume:  133     ISSN:  1095-6433     ISO Abbreviation:  Comp. Biochem. Physiol., Part A Mol. Integr. Physiol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-21     Completed Date:  2003-06-25     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9806096     Medline TA:  Comp Biochem Physiol A Mol Integr Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  661-6     Citation Subset:  IM    
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, MD 20892-1603, USA.
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MeSH Terms
Epithelial Cells / physiology*
Kidney Medulla / cytology,  physiology*
Osmotic Pressure
Water-Electrolyte Balance / physiology*

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