Document Detail

Modeling ischemia in vitro: selective depletion of adenine and guanine nucleotide pools.
MedLine Citation:
PMID:  11003607     Owner:  NLM     Status:  MEDLINE    
Intracellular ATP depletion is a hallmark event in ischemic injury. It has been extensively characterized in models of chemical anoxia in vitro. In contrast, the fate of GTP during ischemia remains unknown. We used LLC-PK proximal tubular cells to measure GTP and ATP changes during anoxia. In 45 min, antimycin A decreased ATP and GTP to 8% and 2% of controls, respectively. Ischemia in vivo resulted in comparable reductions in GTP and ATP. After 2 h of recovery, GTP levels in LLC-PK cells increased to 65% while ATP increased to 29%. We also investigated steady-state models of selective ATP or GTP depletion. Combinations of antimycin A and mycophenolic acid selectively reduced GTP to 51% or 25% of control. Similarly, alanosine selectively reduced ATP to 61% or 26% of control. Selective GTP depletion resulted in significant apoptosis. Selective ATP depletion caused mostly necrosis. These models of ATP or GTP depletion can prove useful in dissecting the relative contribution of the two nucleotides to the ischemic phenotype.
P C Dagher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  279     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-10-12     Completed Date:  2000-10-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  C1270-7     Citation Subset:  IM    
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
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MeSH Terms
Adenosine Triphosphate / metabolism*
Alanine / analogs & derivatives,  pharmacology
Antibiotics, Antineoplastic / pharmacology
Antimycin A / pharmacology
Apoptosis / drug effects
Cell Hypoxia / drug effects
Cells, Cultured
Deoxyglucose / pharmacology
Enzyme Inhibitors / pharmacology
Guanosine / metabolism,  pharmacology
Guanosine Triphosphate / metabolism*
Ischemia / metabolism*
Kidney Cortex / blood supply*,  chemistry
Kidney Tubules, Proximal / cytology,  metabolism*
LLC-PK1 Cells
Models, Biological
Mycophenolic Acid / pharmacology
Oxidative Phosphorylation / drug effects
Rats, Sprague-Dawley
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Enzyme Inhibitors; 118-00-3/Guanosine; 154-17-6/Deoxyglucose; 24280-93-1/Mycophenolic Acid; 56-41-7/Alanine; 56-65-5/Adenosine Triphosphate; 5854-93-3/alanosine; 642-15-9/Antimycin A; 86-01-1/Guanosine Triphosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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