Document Detail

Cell cycle delay and apoptosis in response to osmotic stress.
MedLine Citation:
PMID:  11913454     Owner:  NLM     Status:  MEDLINE    
As part of the urinary concentrating mechanism, renal inner medulla cells may be exposed to extremely variable NaCl and urea concentrations that can reach very high levels. A number of studies, reviewed herein, aim to understand how such osmotic stress affects the cells and what protective mechanisms might exist. The majority of these studies are done on inner medullary epithelial cells that grow continuously in tissue culture (mIMCD3). Cells grown at 300 mosmol/kg survive increase to 500 mosmol/kg by adding NaCl or urea, but only after a growth arrest of approximately 24 h. At a higher osmolality (650-700 mosmol/kg) most cells die within hours by apoptosis. The cells both in vitro and in vivo adapt to high osmolality by a number of mechanisms, including accumulation of variety of organic osmolytes and induction of heat shock proteins. The cell cycle delay results from blocks at the G1 and G2/M checkpoints and slowing during S. After adding NaCl, but not urea, the amount and transcriptional activity of p53 (the tumor suppressor protein) increases. The p53 is phosphorylated on ser-15 and is transcriptionally active at 500 mosmol/kg (associated with cell survival), but not at 700 mosmol/kg (associated with apoptosis). Reduction of p53 expression by p53 antisense oligonucleotide increases sensitivity of renal cells in culture to hyperosmotic stress caused by NaCl. The possible mechanisms of the protection action of p53 against hypertonic stress are discussed.
N I Dmitrieva; L F Michea; G M Rocha; M 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:  130     ISSN:  1095-6433     ISO Abbreviation:  Comp. Biochem. Physiol., Part A Mol. Integr. Physiol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2002-03-26     Completed Date:  2002-04-18     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  9806096     Medline TA:  Comp Biochem Physiol A Mol Integr Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  411-20     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
Cell Cycle*
Osmotic Pressure*
Sodium Chloride / metabolism
Tumor Suppressor Protein p53 / biosynthesis
Reg. No./Substance:
0/Tumor Suppressor Protein p53; 7647-14-5/Sodium Chloride

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