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Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice.


ABSTRACT: 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 eIF2? (eukaryotic translation initiation factor 2?) 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.

SUBMITTER: Peng W 

PROVIDER: S-EPMC3535286 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice.

Peng Wei W   Robertson Lauren L   Gallinetti Jordan J   Mejia Pedro P   Vose Sarah S   Charlip Allison A   Chu Timothy T   Mitchell James R JR  

Science translational medicine 20120101 118


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 1  ...[more]

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