Document Detail

Extracellular glutamine is a critical modulator for regulatory volume increase in human glioma cells.
MedLine Citation:
PMID:  17320059     Owner:  NLM     Status:  MEDLINE    
Mammalian cells regulate their volume to prevent unintentional changes in intracellular signaling, cell metabolism, and DNA integrity. Intentional cell volume changes occur as cells undergo proliferation, apoptosis, or cell migration. To regulate cell volume, cells use channels and transport systems to flux osmolytes across the plasma membrane followed by the obligatory movement of water. While essentially all cells are capable of regulatory volume decrease (RVD), regulatory volume increase (RVI) mechanisms have only been reported in some cell types. In this investigation, we used human glioma cells as a model system to determine conditions necessary for RVI. When exposed to hyperosmotic conditions through the addition of 30 mosM NaCl or sucrose, D54-MG and U251 glioma cell lines and glioma cells from acute patient biopsies shrunk transiently but were able to fully recover their original cell volume within 40-70 min. This ability was highly temperature sensitive and absolutely required the presence of low millimolar concentrations of l-glutamine in the extracellular solution. Other known substrates of glutamine transporters such as methyl-amino isobutyric acid (MeAIB), alanine, and threonine were unable to support RVI. The ability of cells to undergo RVI also required the presence of Na+, K+, and Cl- and was inhibited by the NKCC inhibitor, bumetanide, consistent with the involvement of a Na+/K+/2Cl- cotransporter (NKCC). Moreover, the expression of NKCC1 was demonstrated by Western blot. We concluded that regulatory volume increase in human glioma cells occurs through the uptake of Na+, K+, and Cl- by NKCC1 and is modulated by the presence of glutamine.
Nola Jean Ernest; Harald Sontheimer
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Publication Detail:
Type:  Journal Article     Date:  2007-01-30
Journal Detail:
Title:  Brain research     Volume:  1144     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-06-13     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  231-8     Citation Subset:  IM    
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MeSH Terms
Blotting, Western / methods
Bumetanide / pharmacology
Cell Line, Tumor
Cell Size
Extracellular Space / drug effects,  metabolism*
Gene Expression / drug effects
Glioblastoma / metabolism*,  pathology*
Hypertonic Solutions / pharmacology
Sodium Potassium Chloride Symporter Inhibitors / pharmacology
Sodium-Potassium-Chloride Symporters / metabolism
Solute Carrier Family 12, Member 2
Grant Support
Reg. No./Substance:
0/Hypertonic Solutions; 0/SLC12A2 protein, human; 0/Sodium Potassium Chloride Symporter Inhibitors; 0/Sodium-Potassium-Chloride Symporters; 0/Solute Carrier Family 12, Member 2; 0Y2S3XUQ5H/Bumetanide

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