2013
DOI: 10.1038/labinvest.2012.173
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GCN2 kinase is a key regulator of fibrogenesis and acute and chronic liver injury induced by carbon tetrachloride in mice

Abstract: General control nonderepresible 2 (GCN2) is a highly conserved cytosolic kinase that modulates a complex response for coping with the stress owing to lack of amino acids. GCN2 has been recently shown to be involved in the regulation of metabolic balance and lipid degradation rate in the liver. We hypothesized that GCN2 could have a role in in hepatic fibrogenesis and in the response to acute or chronic liver injury. Activation of GCN2 in primary or immortalized human hepatic stellate cells by incubation with m… Show more

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Cited by 12 publications
(6 citation statements)
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“…43 EIF2AK4 (À/À) knockout mice have been shown to display increased susceptibility to both acute or chronic liver damage induced by carbon tetrachloride, which is accompanied by increased necrosis and greater inflammatory infiltrates compared to wild-type mice. 44 Interestingly, we also noted a pronounced vasculitis of small pulmonary veins in CP-exposed animals. Because only a minority of patients treated with alkylating agents will develop PVOD, further studies on genetic susceptibility and the role of GCN2 in human chemotherapyeinduced PVOD are required.…”
Section: Discussionsupporting
confidence: 51%
“…43 EIF2AK4 (À/À) knockout mice have been shown to display increased susceptibility to both acute or chronic liver damage induced by carbon tetrachloride, which is accompanied by increased necrosis and greater inflammatory infiltrates compared to wild-type mice. 44 Interestingly, we also noted a pronounced vasculitis of small pulmonary veins in CP-exposed animals. Because only a minority of patients treated with alkylating agents will develop PVOD, further studies on genetic susceptibility and the role of GCN2 in human chemotherapyeinduced PVOD are required.…”
Section: Discussionsupporting
confidence: 51%
“…Previous studies by our lab and others indicate that GCN2 serves to protect the liver during asparaginase treatment 6, 10–12 and chronic liver injury by carbon tetrachloride 26 . Based on this scientific premise, our objective was to determine the role of ATF4 in mediating hepatic AAR activation, reduced mTORC1 signaling and liver protection during asparaginase.…”
Section: Introductionmentioning
confidence: 76%
“…) are more susceptible to acute and chronic liver toxicity induced by carbon tetrachloride and increased oxidative stress appears to be a potentially relevant mechanism [31]. GCN2 −/− animals have lower levels of glutathionine peroxidase in the liver [32] and GCN2 activation has antioxidant effects on hepatocytes leading to a decrease in hydrogen peroxide levels [33].…”
Section: Discussionmentioning
confidence: 99%