Ca(2+) rise within a narrow window of concentration prevents functional injury of mitochondria exposed to hypoxia/reoxygenation by increasing antioxidative defence.
Injury of liver by ischaemia crucially involves mitochondrial damage. The role of Ca(2+) in mitochondrial damage is still unclear. We investigated the effect of low micromolar Ca(2+) concentrations on respiration, membrane permeability, and antioxidative defence in liver mitochondria exposed to hypoxia/reoxygenation. Hypoxia/reoxygenation caused decrease in state 3 respiration and in the respiratory control ratio. Liver mitochondria were almost completely protected at about 2 microM Ca(2+). Below and above 2 microM Ca(2+), mitochondrial function was deteriorated, as indicated by the decrease in respiratory control ratio. Above 2 microM Ca(2+), the mitochondrial membrane was permeabilized, as demonstrated by the sensitivity of state 3 respiration to NADH. Below 2 microM Ca(2+), the nitric oxide synthase inhibitor nitro-l-arginine methylester had a protective effect. The activities of the manganese superoxide dismutase and glutathione peroxidase after hypoxia showed maximal values at about 2 microM Ca(2+). We conclude that Ca(2+) exerts a protective effect on mitochondria within a narrow concentration window, by increasing the antioxidative defence.
Schild
Lorenz
L
Bereich Pathologische Biochemie der Medizinischen Fakultät der Otto-von-Guericke-Universität Magdeburg, Germany. lorenz.schild@medizin.uni-magdeburg.de
Plumeyer
Frank
F
Reiser
Georg
G
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D011506:Proteins; D009243:NAD; D016572:Cyclosporine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010100:Oxygen; D002118:Calcium