Effect of a ubiquinone-like molecule on oxidative energy metabolism in rat cortical synaptosomes at different ages.
Persistent stimulation of energy consumption, induced by depolarization with veratridine, mimics a condition of abnormally enhanced energy demand and causes an increase in the oxygen consumption rate (QO2) and in the interconversion of pyruvate dehydrogenase complex (PDHc) into its active form. Wistar rats at the age of 26 months do not show alterations of QO2 and the ability of veratridine to increase QO2 in comparison with 6 month-old animals whereas the active form of PDHc is slightly but significantly reduced. Idebenone, a ubiquinone-like molecule (1 microM), does not affect the QO2 or PDHc activation state in resting conditions but attenuates the veratridine-challenged increase in QO2 at all the ages tested and attenuates the increase in the percentage of PDHa reaching statistical significance in 26-month-old rats. At higher concentration (10 microM) idebenone totally abolishes the veratridine-induced increase in PDHa also in the 6 month-old rats. At the lower concentration, the drug does not affect the increase in QO2 induced by an uncoupler of oxidative phosphorylation. The results obtained suggest a protective effect of idebenone on the cerebral tissue against stressful conditions; this action may be exerted at the level of some mitochondrial component and/or on the Na+ homeostasis.
Curti
D
D
Institute of Pharmacology, Faculty of Sciences, University of Pavia, Italy.
Izzo
E
E
Brambilla
L
L
Facchetti
G
G
Sangiovanni
G
G
Brambilla
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation; D008297:Male; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011768:Pyruvate Dehydrogenase Complex / Q000819:agonists; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014451:Ubiquinone / Q000494:pharmacology* / Q000031:analogs & derivatives; D014701:Veratridine / Q000494:pharmacology
D016227:Benzoquinones; D011768:Pyruvate Dehydrogenase Complex; D014451:Ubiquinone; D014701:Veratridine; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; C036619:idebenone