Abstract
The protective effects of paeoniflorin isolated from Paeonia lactiflora against pharmacological inhibition of the respiratory chain were studied using osteoblastic MC3T3-E1 cells. Here we show that paeoniflorin decreases cell death induced by antimycin A, an inhibitor of mitochondrial complex III. Paeoniflorin restored antimycin A-induced inactivation of phosphoinositide 3-kinase (PI3K) and thioredoxin reductase, suggesting that PI3K and thioredoxin reductase may be involved in paeoniflorin-induced cytoprotective responses. We also examined the effect of paeoniflorin on mitochondrial dysfunction and oxidative stress induced by antimycin A. Paeoniflorin inhibited mitochondrial membrane potential dissipation, ATP loss, inactivation of complexes I and IV, cytochrome c release, and cardiolipin oxidation induced by antimycin A. In addition, paeoniflorin prevented antimycin A-induced ROS release and nitrotyrosine increase. These results imply that paeoniflorin protects osteoblasts from antimycin A-induced cell death via improved mitochondrial function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Antimycin A / adverse effects*
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Antioxidants / pharmacology
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Benzoates / pharmacology*
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Bridged-Ring Compounds / pharmacology*
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Cardiolipins / metabolism
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Cell Survival
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Cytochromes c / metabolism
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Glucosides / pharmacology*
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Membrane Potential, Mitochondrial / drug effects
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Mice
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Mitochondria / drug effects
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Monoterpenes
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Osteoblasts / cytology
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Osteoblasts / drug effects*
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Oxidative Stress / drug effects
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Paeonia / chemistry*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Plant Extracts / pharmacology
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Protective Agents / pharmacology
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Reactive Oxygen Species / metabolism
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Thioredoxin-Disulfide Reductase / antagonists & inhibitors
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Thioredoxin-Disulfide Reductase / metabolism
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Tumor Necrosis Factor-alpha / metabolism
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Tyrosine / analogs & derivatives
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Tyrosine / metabolism
Substances
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Antioxidants
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Benzoates
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Bridged-Ring Compounds
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Cardiolipins
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Glucosides
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Monoterpenes
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Phosphoinositide-3 Kinase Inhibitors
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Plant Extracts
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Protective Agents
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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peoniflorin
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3-nitrotyrosine
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Tyrosine
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Antimycin A
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Cytochromes c
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Thioredoxin-Disulfide Reductase