| Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice. | |
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MedLine Citation:
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PMID: 22277968 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Wei Peng; Lauren Robertson; Jordan Gallinetti; Pedro Mejia; Sarah Vose; Allison Charlip; Timothy Chu; James R Mitchell |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science translational medicine Volume: 4 ISSN: 1946-6242 ISO Abbreviation: Sci Transl Med Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-01-26 Completed Date: 2012-09-13 Revised Date: 2013-05-10 |
Medline Journal Info:
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Nlm Unique ID: 101505086 Medline TA: Sci Transl Med Country: United States |
Other Details:
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Languages: eng Pagination: 118ra11 Citation Subset: IM |
Affiliation:
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Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dietary Proteins / metabolism Humans Kidney / blood supply, drug effects, pathology Liver / blood supply, drug effects, pathology Mice 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 | |
ID/Acronym/Agency:
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AG036712/AG/NIA NIH HHS; DK090629/DK/NIDDK NIH HHS; R01 AG036712/AG/NIA NIH HHS; R01 DK090629/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Proteins; 0/Piperidines; 0/Quinazolinones; 147-85-3/Proline; 73-22-3/Tryptophan; EC 2.7.11.1/Eif2ak4 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; L31MM1385E/halofuginone |
| Comments/Corrections | |
Comment In:
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Sci Transl Med. 2012 Mar 7;4(124):124ps6
[PMID:
22399263
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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