Document Detail

Chronic intermittent hypoxia decreases the expression of Na/H exchangers and HCO3-dependent transporters in mouse CNS.
MedLine Citation:
PMID:  12665539     Owner:  NLM     Status:  MEDLINE    
Chronic intermittent hypoxia (CIH) is a component of several disease states, including obstructive sleep apnea, which results in neurocognitive and cardiovascular morbidity. Because chronic hypoxia can induce changes in metabolism and pH homeostasis, we hypothesized that CIH induces changes in the expression of acid-base transporters. Two- to three-day-old mice, exposed to alternating cycles of 2 min of hypoxia (6.0-7.5% O2) and 3 min of normoxia (21% O2) for 8 h/day for 28 days, demonstrated decreases in specific acid-base transport protein expression in most of the central nervous system (CNS). Sodium/hydrogen exchanger isoform 1 (NHE1) and sodium-bicarbonate cotransporter expression were decreased in all regions of the CNS but especially so in the cerebellum. NHE3, which is only expressed in the cerebellum, was also significantly decreased. Anion exchanger 3 protein was decreased in most brain regions, with the decrease being substantial in the hippocampus. These results indicate that CIH induces downregulation of the major acid-extruding transport proteins, NHE1 and sodium-bicarbonate cotransporter, in particular regions of the CNS. This downregulation in acid-extruding capacity may render neurons more prone to acidity and possibly to injury during CIH, especially in the cerebellum and hippocampus. Alternatively, it is possible that O2 consumption in these regions is decreased after CIH, with consequential downregulation in the expression of certain cellular proteins that may be less needed under such circumstances.
R M Douglas; J Xue; J Y Chen; C G Haddad; S L Alper; G G Haddad
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-03-28
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  95     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-09     Completed Date:  2004-02-02     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  292-9     Citation Subset:  IM    
Department of Respiratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
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MeSH Terms
Acid-Base Equilibrium / physiology
Anoxia / enzymology,  metabolism*
Bicarbonates / metabolism*
Blotting, Western
Carrier Proteins / metabolism*
Central Nervous System / metabolism*
Cerebellum / metabolism
Chronic Disease
Hippocampus / metabolism
Sodium-Hydrogen Antiporter / biosynthesis*,  metabolism
Grant Support
Reg. No./Substance:
0/Bicarbonates; 0/Carrier Proteins; 0/Sodium-Hydrogen Antiporter; 0/growth factor-activatable Na-H exchanger NHE-1; 0/sodium-hydrogen exchanger 3

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