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Activation of the mitochondrial ATP-sensitive K+ channel reduces apoptosis of spleen mononuclear cells induced by hyperlipidemia
- Source :
- Lipids in Health and Disease
- Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 1476511X
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Lipids in health and disease
- Accession number :
- edsair.doi.dedup.....7a7368461cc30a210c2a9367ab0522cc