Ca2+-stimulated mitochondrial reactive oxygen species generation and permeability transition are inhibited by dibucaine or Mg2+. 1998

A J Kowaltowski, and E S Naia-da-Silva, and R F Castilho, and A E Vercesi
Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, 13083-970, Brazil. alicia@obelix.unicamp.br

Mitochondrial swelling and membrane protein thiol oxidation associated with mitochondrial permeability transition induced by Ca2+ and t-butyl hydroperoxide or inorganic phosphate, but not 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid or phenylarsine oxide, are inhibited by the local anesthetic dibucaine. Dibucaine promotes an inhibition of the Ca2+-induced increase in mitochondrial H2O2 generation measured by the oxidation of scopoletin in the presence of horseradish peroxidase. This decrease in mitochondrial H2O2 generation may be attributed to the reduction of Ca2+ binding to the membrane induced by dibucaine, as assessed by measuring 45Ca2+ binding to the mitochondrial membrane. Mg2+ also inhibited Ca2+ binding to the mitochondrial membrane, mitochondrial swelling, membrane protein thiol oxidation, and H2O2 generation induced by Ca2+. Together, these results demonstrate that the mechanism by which dibucaine and Mg2+ inhibit mitochondrial permeability transition is related to the decrease in reactive oxygen species generation induced by Ca2+-promoted alterations of inner mitochondrial membrane properties.

UI MeSH Term Description Entries
D007425 Intracellular Membranes Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES. Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D008274 Magnesium A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D003992 Dibucaine A local anesthetic of the amide type now generally used for surface anesthesia. It is one of the most potent and toxic of the long-acting local anesthetics and its parenteral use is restricted to spinal anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1006) Cincain,Cinchocaine,Nupercainal,Nupercaine,Sovcaine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding

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