Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition
Autor: | Pamela Martinis, Antonio Toninello, Silvia Grancara, M. Maritati, Enzo Agostinelli, Marcantonio Bragadin, Valentina Battaglia, L. Zago, Valeria Rizzoli |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Clinical Biochemistry
Apoptosis Mitochondria Liver melatonin Oxidative phosphorylation Biology Mitochondrion Membrane Potential Biochemistry Permeability Melatonin chemistry.chemical_compound pro-apoptotic factors Cyclosporin a medicine Animals oxidative stress Membrane Potential Mitochondrial Membrane potential mitochondria permeability transition Ca2+ Cytochrome c Organic Chemistry Apoptosis Inducing Factor Cytochromes c Hydrogen Peroxide Glutathione Mitochondrial Rats Cell biology Liver Mitochondrial permeability transition pore chemistry Mitochondrial Membranes Cyclosporine biology.protein Ca 2+ Mitochondria Oxidative stress Permeability transition Pro-apoptotic factors Calcium Energy Metabolism Oxidative Stress medicine.drug |
Popis: | Melatonin, a metabolic product of the amino acid tryptophan, induces a dose-dependent energy drop correlated with a decrease in the oxidative phosphorylation process in isolated rat liver mitochondria. This effect involves a gradual decrease in the respiratory control index and significant alterations in the state 4/state 3 transition of membrane potential (ΔΨ). Melatonin, alone, does not affect the insulating properties of the inner membrane but, in the presence of supraphysiological Ca2+, induces a ΔΨ drop and colloid-osmotic mitochondrial swelling. These events are sensitive to cyclosporin A and the inhibitors of Ca2+ transport, indicative of the induction or amplification of the mitochondrial permeability transition. This phenomenon is triggered by oxidative stress induced by melatonin and Ca2+, with the generation of hydrogen peroxide and the consequent oxidation of sulfydryl groups, glutathione and pyridine nucleotides. In addition, melatonin, again in the presence of Ca2+, can also induce substantial release of cytochrome C and AIF (apoptosis-inducing factor), thus revealing its potential as a pro-apoptotic agent. |
Databáze: | OpenAIRE |
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