Dehydroascorbic acid as pre-conditioner: protection from lipopolysaccharide induced mitochondrial damage.
Oxidative stress-induced mitochondrial dysfunction is a common consequence of severe sepsis. However, oxidative stress also activates signalling cascades which enable protection of cells against subsequent oxidative damage. This study hypothesized that cellular uptake of vitamin C as dehydroascorbic acid rather than ascorbic acid would up-regulate antioxidant enzyme systems and impart a protective effect to mitochondria in cells subsequently exposed to lipopolysaccharide (LPS) in an iron free environment. Treatment of monocytes with dehydroascorbic acid, but not ascorbic acid, caused oxidative stress (p< 0.001). Dehydroascorbic acid exposure also resulted in increased manganese superoxide dismutase (p= 0.018) and catalase (p= 0.003) expression. Pre-treatment of monocytes with dehydroascorbic acid followed by LPS resulted in higher mitochondrial membrane potentials than cells without pre-treatment (p< 0.0001). Lower cytochrome c in cytosol (p< 0.05) and higher mitochondrial expression of the anti-apoptotic Bcl-2 protein (p= 0.029) was also found in monocytes pre-treated before subsequent LPS exposure, compared to cells without pre-treatment. In conclusion, acute exposure of monocytes to dehydroascorbic acid in an iron free environment induces cytoprotective antioxidant enzymes and protected mitochondria from the harmful effects of oxidative stress prior to a septic insult, which was abrogated when cells were pre-incubated with the DHA uptake inhibitor cytocholasin B.
Lowes
Damon A
DA
Division of Applied Medicine, School of Medicine & Dentistry, University of Aberdeen, UK.
Webster
Nigel R
NR
Galley
Helen F
HF
D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002374:Catalase / Q000096:biosynthesis; D002469:Cell Separation; D003683:Dehydroascorbic Acid / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000096:biosynthesis
D000975:Antioxidants; D008070:Lipopolysaccharides; D002374:Catalase; D013482:Superoxide Dismutase; D003683:Dehydroascorbic Acid