title: Inhibition of mitochondrial protein synthesis results in increased endothelial cell susceptibility to nitric oxide-induced apoptosis.
abstract: Mutations in mitochondrial DNA, affecting the activity of respiratory complexes, have been implicated in many chronic degenerative diseases. Mitochondrial proteins coded for by both the mitochondrial and nuclear genes are known to have important signaling roles in apoptosis. However, the impact of the inhibition of mitochondrial protein synthesis on apoptosis is largely unknown. This inhibition is particularly important in NO-dependent cytotoxicity, which is believed to have a significant mitochondrial component and depend on other factors such as glycolysis. In this study we have examined whether the inhibition of mitochondrial protein synthesis by chloramphenicol increases the susceptibility of endothelial cells to undergo NO-dependent apoptosis in glucose-free media. Bovine aortic endothelial cells were treated with chloramphenicol, which resulted in a decreased ratio of mitochondrial complex IV to cytochrome c and increased oxidant production in the cell. Inhibition of mitochondrial protein synthesis was associated with a greater susceptibility of the cells to apoptosis induced by NO in glucose-free medium.
authors: Department of Pathology, University of Alabama, Birmingham, AL 35294, USA.
authors: Anup
authors: A
authors: Ramachandran
authors: Douglas R
authors: DR
authors: Moellering
authors: Erin
authors: E
authors: Ceaser
authors: Sruti
authors: S
authors: Shiva
authors: Jun
authors: J
authors: Xu
authors: Victor
authors: V
authors: Darley-Usmar
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000475:Alkenes / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002701:Chloramphenicol / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D042963:Electron Transport Complex II; D004730:Endothelium, Vascular / Q000166:cytology; D004734:Energy Metabolism; D008928:Mitochondria / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D000475:Alkenes; D003574:Cytochrome c Group; D009097:Multienzyme Complexes; D020030:Nitric Oxide Donors; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; C453079:dipropylenetriamine-NONOate; D009569:Nitric Oxide; D002701:Chloramphenicol; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D053148:Caspase 3; D020169:Caspases