Maintenance of oxidative phosphorylation protects cells from Actinobacillus actinomycetemcomitans leukotoxin-induced apoptosis
| Autor: | Irene R. Kieba, Noboru Yamaguchi, Edward T. Lally, Bruce J. Shenker, Pamela S. Howard, Jon Korostoff |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Bacterial Toxins
Immunology bcl-X Protein Exotoxins Gene Expression Apoptosis Cytochrome c Group Oxidative phosphorylation Biology Aggregatibacter actinomycetemcomitans Microbiology Oxidative Phosphorylation Cell Line Adenosine Triphosphate Virology Caspase 7 chemistry.chemical_classification Reactive oxygen species Dose-Response Relationship Drug ATP synthase Caspase 3 Cytotoxins Cytochrome c Transfection Molecular biology Caspase 9 Proto-Oncogene Proteins c-bcl-2 chemistry Mitochondrial matrix Caspases biology.protein Intermembrane space |
| Zdroj: | Cellular Microbiology. 3:811-823 |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1046/j.1462-5822.2001.00161.x |
| Popis: | Subnanomolar concentrations (3 x 10(-10) M) of Actinobacillus actinomycetemcomitans leukotoxin (Ltx) trigger apoptosis of JY cells, as shown by a decrease in mitochondrial transmembrane potential (DeltaPsim), hyperproduction of reactive oxygen species (ROS) and release of cytochrome c from the intermembrane space. When compared with heat-inactivated leukotoxin (DeltaI Ltx) controls, ATP levels in Ltx-treated JY cells continued to decrease during a 24 h experiment while cytoplasmic ADP concentrations were increasing. These results suggest that a blockage occurred in ATP/ADP exchange. To maintain ATP/ADP exchange, JY cells were transfected with bcl-2 and bcl-xL and incubated with Ltx. ATP levels of the transfected cells decreased to 67% (JY/bcl-2) and 73% (JY/bcl-xL) after the experiment. Furthermore, cytochrome c remained localized to the mitochondrial fraction of Ltx-treated JY/bcl-2 and JY/bcl-xL cells, whereas its presence in the cytoplasmic fraction of JY/gen cells suggests an uncoupling of electron transport. Expression of bcl-2 and bcl-xL in cells inhibited downstream apoptotic events such as cleavage of poly(ADP-ribose) polymerase, DNA fragmentation and activation of a family of caspases. The results indicate that Ltx induces apoptosis through a mitochondrial pathway that involves decreased levels of the ADP in the mitochondrial matrix, a lack of substrate for ATP synthetase and arrest of oxidative phosphorylation. |
| Databáze: | OpenAIRE |
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