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Mitochondrial ATP-sensitive K(+) channels as redox signals to liver mitochondria in response to hypertriglyceridemia
- Source :
- Free radical biologymedicine. 47(10)
- Publication Year :
- 2009
-
Abstract
- We have recently demonstrated that hypertriglyceridemic (HTG) mice present both elevated body metabolic rates and mild mitochondrial uncoupling in the liver owing to stimulated activity of the ATP-sensitive potassium channel (mitoK ATP ). Because lipid excess normally leads to cell redox imbalance, we examined the hepatic oxidative status in this model. Cell redox imbalance was evidenced by increased total levels of carbonylated proteins, malondialdehydes, and GSSG/GSH ratios in HTG livers compared to wild type. In addition, the activities of the extramitochondrial enzymes NADPH oxidase and xanthine oxidase were elevated in HTG livers. In contrast, Mn-superoxide dismutase activity and content, a mitochondrial matrix marker, were significantly decreased in HTG livers. Isolated HTG liver mitochondria presented lower rates of H 2 O 2 production, which were reversed by mitoK ATP antagonists. In vivo antioxidant treatment with N -acetylcysteine decreased both mitoK ATP activity and metabolic rates in HTG mice. These data indicate that high levels of triglycerides increase reactive oxygen generation by extramitochondrial enzymes that promote mitoK ATP activation. The mild uncoupling mediated by mitoK ATP increases metabolic rates and protects mitochondria against oxidative damage. Therefore, a biological role for mitoK ATP as a redox sensor is shown here for the first time in an in vivo model of systemic and cellular lipid excess.
- Subjects :
- Male
medicine.medical_specialty
Potassium Channels
Mice, Transgenic
Mitochondria, Liver
Oxidative phosphorylation
Mitochondrion
Biochemistry
chemistry.chemical_compound
Mice
Physiology (medical)
Internal medicine
medicine
Animals
Xanthine oxidase
chemistry.chemical_classification
Hypertriglyceridemia
Reactive oxygen species
NADPH oxidase
biology
Glutathione
Disease Models, Animal
Enzyme
Endocrinology
chemistry
Mitochondrial matrix
biology.protein
Female
Reactive Oxygen Species
Oxidation-Reduction
Subjects
Details
- ISSN :
- 18734596
- Volume :
- 47
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Free radical biologymedicine
- Accession number :
- edsair.doi.dedup.....f70ad8d0494935258669390f2794d63e