Rapid up-regulation of peptide elongation factor EF-1alpha protein levels is an immediate early event during oxidative stress-induced apoptosis.
Hydrogen peroxide (H(2)O(2)) induces apoptosis in cultured cells, in a dose-dependent manner. Treatment with H(2)O(2) causes decreased mitochondrial respiration, along with DNA degradation and the formation of an oligonucleosomal ladder, all hallmarks of apoptotic cell death. In this report, we investigate alterations in expression of a peptide elongation factor, EF-1alpha, during oxidative challenge. EF-1alpha protein levels undergo rapid increase upon treatment with H(2)O(2); however, whereas sublethal doses of H(2)O(2) stimulate only transient increases of EF-1alpha protein levels, lethal doses produce sustained elevation of EF-1alpha levels. Furthermore, pretreatment of H9c2(2-1) cells with transcriptional inhibitors fails to abolish the oxidant-induced increase in EF-1alpha, and Northern blotting analysis reveals that EF-1alpha mRNA levels remain steady throughout the H(2)O(2) treatment period, suggesting that the up-regulation of EF-1alpha is mediated posttranscriptionally. Transient transfection with an antisense EF-1alpha cDNA protects against hydrogen peroxide-mediated cytotoxicity in proportion to the degree of repression of EF-1alpha protein levels, suggesting that up-regulation of EF-1alpha plays a role in expediting the execution of the apoptotic program in response to oxidative stress.
Chen
E
E
Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, The Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec, H3T 1E2, Canada.
Proestou
G
G
Bourbeau
D
D
Wang
E
E
D000199:Actins / Q000378:metabolism; D000818:Animals; D016375:Antisense Elements (Genetics); D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003603:Cytotoxins / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D020648:Peptide Elongation Factor 1 / Q000235:genetics*; D014176:Protein Biosynthesis / Q000502:physiology; D051381:Rats; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection
D000199:Actins; D016375:Antisense Elements (Genetics); D003603:Cytotoxins; D016877:Oxidants; D020648:Peptide Elongation Factor 1; D006861:Hydrogen Peroxide