Document Detail

Protein synthesis inhibition as a potential strategy for metabolic down-regulation.
MedLine Citation:
PMID:  17250947     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: This pilot study tested the potential of puromycin (PUR) to inhibit protein synthesis and reduce oxygen utilization in a non-hibernating, whole animal preparation. METHODS: After anesthesia and instrumentation, male rats received a single dose of PUR or 0.9% saline (control), followed 60 min later with [(35)S] methionine/cysteine radiolabeling. Thirty minutes after isotope injection, organ biopsies were taken for quantification of de novo protein synthesis. Arterial and central venous blood gases were obtained at baseline and 60 min after injection of PUR or 0.9% saline. Temperature, mean arterial pressure (MAP), and heart rate were recorded continuously. RESULTS: Animals receiving PUR demonstrated significant reductions in protein synthesis in all organ systems sampled (p<0.05). The overall reduction averaged 67.8%. Central venous oxygen saturations (S(cv)O(2)) were higher in the PUR group than the controls at 60 min (90+/-2% versus 80+/-4%, p<0.05). The oxygen extraction ratio (O(2)ER) decreased from 16.1+/-1.7% to 6.8+/-1.2% in the PUR group (p<0.05) and increased from 12.5+/-3.2% to 16.0+/-4.2% in the controls (p=0.44). There was no difference in temperature, MAP, heart rate or blood gas variables, other than S(cv)O(2), at baseline or 60 min between groups. CONCLUSIONS: These results demonstrate that PUR is capable of reducing whole body protein synthesis significantly within a relatively short duration of time. This appears to decrease whole body oxygen utilization as evidenced by an increase in S(cv)O(2) and a decrease in O(2)ER. Protein synthesis inhibition may reduce metabolic demands and should be tested for its potential to improve outcomes where oxygen demands exceed oxygen delivery.
Melissa C Evans; Robert F Diegelmann; R Wayne Barbee; M Hakam Tiba; Eric Edwards; Sue Sreedhar; Kevin R Ward
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-01-23
Journal Detail:
Title:  Resuscitation     Volume:  73     ISSN:  0300-9572     ISO Abbreviation:  Resuscitation     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-20     Completed Date:  2007-11-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0332173     Medline TA:  Resuscitation     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  296-303     Citation Subset:  IM    
Department of Pediatrics, Division of Pediatric Critical Care, VCUHS, P.O. Box 980530, Richmond, VA 23298-0530, USA. <>
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MeSH Terms
Blood Gas Analysis
Down-Regulation / drug effects*
Oxygen Consumption / drug effects
Proteins / metabolism*
Puromycin / pharmacology*
Rats, Sprague-Dawley
Shock / physiopathology
Grant Support
5T32GM008695-04/GM/NIGMS NIH HHS; K08 HD049616-01A2/HD/NICHD NIH HHS
Reg. No./Substance:
0/Proteins; 53-79-2/Puromycin

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

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