RGD Reference Report - A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death. - Rat Genome Database

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A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death.

Authors: Borradaile, NM  Buhman, KK  Listenberger, LL  Magee, CJ  Morimoto, ET  Ory, DS  Schaffer, JE 
Citation: Borradaile NM, etal., Mol Biol Cell. 2006 Feb;17(2):770-8. Epub 2005 Nov 30.
RGD ID: 10401198
Pubmed: PMID:16319173   (View Abstract at PubMed)
PMCID: PMC1356587   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E05-08-0742   (Journal Full-text)

The deleterious consequences of fatty acid (FA) and neutral lipid accumulation in nonadipose tissues, such as the heart, contribute to the pathogenesis of type 2 diabetes. To elucidate mechanisms of FA-induced cell death, or lipotoxicity, we generated Chinese hamster ovary (CHO) cell mutants resistant to palmitate-induced death and isolated a clone with disruption of eukaryotic elongation factor (eEF) 1A-1. eEF1A-1 involvement in lipotoxicity was confirmed in H9c2 cardiomyoblasts, in which small interfering RNA-mediated knockdown also conferred palmitate resistance. In wild-type CHO and H9c2 cells, palmitate increased reactive oxygen species and induced endoplasmic reticulum (ER) stress, changes accompanied by increased eEF1A-1 expression. Disruption of eEF1A-1 expression rendered these cells resistant to hydrogen peroxide- and ER stress-induced death, indicating that eEF1A-1 plays a critical role in the cell death response to these stressors downstream of lipid overload. Disruption of eEF1A-1 also resulted in actin cytoskeleton defects under basal conditions and in response to palmitate, suggesting that eEF1A-1 mediates lipotoxic cell death, secondary to oxidative and ER stress, by regulating cytoskeletal changes critical for this process. Furthermore, our observations of oxidative stress, ER stress, and induction of eEF1A-1 expression in a mouse model of lipotoxic cardiomyopathy implicate this cellular response in the pathophysiology of metabolic disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of apoptotic process  IMP 10401198 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Eef1a1  (eukaryotic translation elongation factor 1 alpha 1)


Additional Information