Activation of the mitochondrial ATP-sensitive K+ channel reduces apoptosis of spleen mononuclear cells induced by hyperlipidemia
| Autor: | Helena C. F. Oliveira, Bruno A. Paim, Luciane C. Alberici, Karina G. Zecchin, Sandra R. Mirandola, Roger F. Castilho, Cezar R. Pestana, Anibal E. Vercesi |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Programmed cell death
Potassium Channels Endocrinology Diabetes and Metabolism Clinical Biochemistry Apoptosis Hyperlipidemias Mitochondrion medicine.disease_cause Peripheral blood mononuclear cell chemistry.chemical_compound Mice Endocrinology Adenosine Triphosphate Oxygen Consumption Superoxides medicine Animals Biochemistry medical chemistry.chemical_classification Hypertriglyceridemia Reactive oxygen species biology Superoxide Cytochrome c Research Biochemistry (medical) Leukopenia Mitochondria uncoupling Cell biology Mitochondria Oxidative Stress Biochemistry chemistry biology.protein Leukocytes Mononuclear Cell redox state Reactive Oxygen Species Oxidative stress Spleen |
| Zdroj: | Lipids in Health and Disease |
| ISSN: | 1476-511X |
| Popis: | Background We have previously demonstrated that increased rates of superoxide generation by extra-mitochondrial enzymes induce the activation of the mitochondrial ATP-sensitive potassium channel (mitoKATP) in the livers of hypertriglyceridemic (HTG) mice. The resulting mild uncoupling mediated by mitoKATP protects mitochondria against oxidative damage. In this study, we investigate whether immune cells from HTG mice also present increased mitoKATP activity and evaluate the influence of this trait on cell redox state and viability. Methods Oxygen consumption (Clark-type electrode), reactive oxygen species production (dihydroethidium and H2-DCF-DA probes) and cell death (annexin V, cytocrome c release and Trypan blue exclusion) were determined in spleen mononuclear cells. Results HTG mice mononuclear cells displayed increased mitoKATP activity, as evidenced by higher resting respiration rates that were sensitive to mitoKATP antagonists. Whole cell superoxide production and apoptosis rates were increased in HTG cells. Inhibition of mitoKATP further increased the production of reactive oxygen species and apoptosis in these cells. Incubation with HTG serum induced apoptosis more strongly in WT cells than in HTG mononuclear cells. Cytochrome c release into the cytosol and caspase 8 activity were both increased in HTG cells, indicating that cell death signaling starts upstream of the mitochondria but does involve this organelle. Accordingly, a reduced number of blood circulating lymphocytes was found in HTG mice. Conclusions These results demonstrate that spleen mononuclear cells from hyperlipidemic mice have more active mitoKATP channels, which downregulate mitochondrial superoxide generation. The increased apoptosis rate observed in these cells is exacerbated by closing the mitoKATP channels. Thus, mitoKATP opening acts as a protective mechanism that reduces cell death induced by hyperlipidemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink