Chlamydia (Chlamydophila) pneumoniae-induced cell death in human coronary artery endothelial cells is caspase-independent and accompanied by subcellular translocations of Bax and apoptosis-inducing factor.
Atherosclerosis and coronary heart disease are causing high morbidity and mortality worldwide. Different risk factors have been demonstrated, but the exact mechanisms behind these diseases are still not fully understood. Recent studies have suggested Chlamydia pneumoniae to be involved in the pathogenesis, and increased apoptotic indexes in atherosclerotic plaques have been documented. In this study, we show that C. pneumoniae induces apoptosis and necrosis in populations of human coronary artery endothelial cells. Apoptosis was determined by TUNEL and flow cytometry after staining of cells with annexin V and propidium iodide, and defined as TUNEL-reactive or annexin V-positive, propidium iodide-negative cells. The apoptosis was induced within 2 h postinfection and increased with inoculation dose. The general caspase inhibitor z-VAD-fmk did not affect apoptotic frequencies. By immunochemistry and immunoblot, we demonstrated activation and subcellular translocation of the proapoptotic protein Bax, and translocation of apoptosis-inducing factor from the cytosol to the nucleus. These results indicate that C. pneumoniae-induced apoptosis in human coronary artery endothelial cells is caspase-independent and regulated by Bax and apoptosis-inducing factor.
Schöier
Johan
J
Department of Molecular and Clinical Medicine, Division of Clinical Microbiology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Högdahl
Marie
M
Söderlund
Gustaf
G
Kihlström
Erik
E
D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D023521:Chlamydophila Infections / Q000378:metabolism / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D051033:Apoptosis Inducing Factor; D051028:bcl-2-Associated X Protein; D020169:Caspases