Document Detail

Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice.
MedLine Citation:
PMID:  22277968     Owner:  NLM     Status:  MEDLINE    
Dietary restriction, or reduced food intake without malnutrition, increases life span, health span, and acute stress resistance in model organisms from yeast to nonhuman primates. Although dietary restriction is beneficial for human health, this treatment is not widely used in the clinic. Here, we show that short-term, ad libitum feeding of diets lacking essential nutrients increased resistance to surgical stress in a mouse model of ischemia reperfusion injury. Dietary preconditioning by 6 to 14 days of total protein deprivation, or removal of the single essential amino acid tryptophan, protected against renal and hepatic ischemic injury, resulting in reduced inflammation and preserved organ function. Pharmacological treatment with halofuginone, which activated the amino acid starvation response within 3 days by mimicking proline deprivation, was also beneficial. Both dietary and pharmacological interventions required the amino acid sensor and eIF2α (eukaryotic translation initiation factor 2α) kinase Gcn2 (general control nonderepressible 2), implicating the amino acid starvation response and translational control in stress protection. Thus, short-term dietary or pharmacological interventions that modulate amino acid sensing can confer stress resistance in models of surgical ischemia reperfusion injury.
Wei Peng; Lauren Robertson; Jordan Gallinetti; Pedro Mejia; Sarah Vose; Allison Charlip; Timothy Chu; James R Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science translational medicine     Volume:  4     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-26     Completed Date:  2012-09-13     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  118ra11     Citation Subset:  IM    
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
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MeSH Terms
Dietary Proteins / metabolism
Kidney / blood supply,  drug effects,  pathology
Liver / blood supply,  drug effects,  pathology
Mice, Inbred C57BL
Organ Specificity / drug effects
Piperidines / pharmacology
Proline / pharmacology
Protein Deficiency / complications,  pathology
Protein-Serine-Threonine Kinases / metabolism*
Quinazolinones / pharmacology
Reperfusion Injury / complications,  pathology,  prevention & control*,  surgery*
Stress, Physiological* / drug effects
Tryptophan / deficiency*,  metabolism
Grant Support
Reg. No./Substance:
0/Dietary Proteins; 0/Piperidines; 0/Quinazolinones; 147-85-3/Proline; 73-22-3/Tryptophan; EC protein, mouse; EC Kinases; L31MM1385E/halofuginone
Comment In:
Sci Transl Med. 2012 Mar 7;4(124):124ps6   [PMID:  22399263 ]

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