Effects of the general anaesthetic Propofol on the Ca2(+)-induced permeabilization of rat liver mitochondria.
The molecular mechanism of the Ca2(+)-induced permeabilization of rat liver mitochondria was evaluated by studying a new effect of the commonly used general anaesthetic Propofol (2,6-diisopropylphenol). The compound was found to induce an apparent uptake of Ca2+ at steady-state in the Ca2(+)-distribution between the medium and the mitochondria, and to inhibit swelling and release of accumulated Ca2+ induced by inorganic phosphate, t-butyl hydroperoxide, diamide or FCCP plus Ruthenium red. The compound did not stimulate the activity of the Ca2(+)-uniporter and it is concluded that the effects seen are due to the inhibition of the Ca2(+)-dependent, unspecific permeability increase. The results suggest two mechanisms whereby Propofol stabilizes the mitochondrial membrane in the presence of Ca2+: (i) by interaction with the putative pore, thus causing its closure; and (ii) by scavenging of free radicals thus inhibiting its opening during oxidative stress.
Eriksson
O
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Department of Medical Chemistry, University of Helsinki, Finland.
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D012430:Ruthenium Red; D002084:Butylated Hydroxytoluene; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D020122:tert-Butylhydroperoxide; D002118:Calcium; D015742:Propofol