Inhibition of glycerophosphate-dependent H2O2 generation in brown fat mitochondria by idebenone.
The established protective effect of coenzyme Q (CoQ) analogs is dependent on the location of reactive oxygen species (ROS) generation. One of these analogs--idebenone (hydroxydecyl-ubiquinone) is used as an antioxidative therapeutic drug. We tested its scavenging effect on the glycerophosphate (GP)-dependent ROS production as this enzyme was shown as a new site in the mitochondrial respiratory chain where ROS can be generated. We observed that idebenone inhibits both GP- and succinate-dependent ROS production. Idebenone and CoQ1 were found to be more efficient in the scavenging activity (IC50: 0.052 and 0.075 microM, respectively) than CoQ3 (IC50: 45.8 microM). Idebenone also inhibited ferricyanide (FeCN)-activated, GP-dependent ROS production. Our data thus extend previous findings on the scavenging effect of idebenone and show that it can also eliminate GP-dependent ROS generation.
Rauchová
Hana
H
Institute of Physiology, Academy of Sciences of the Czech Republic, Czech Republic. rauchova@biomed.cas.cz
Vrbacký
Marek
M
Bergamini
Christian
C
Fato
Romana
R
Lenaz
Giorgio
G
Houstek
Josef
J
Drahota
Zdenek
Z
D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D006224:Cricetinae; D005292:Ferricyanides / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005994:Glycerophosphates / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism / Q000031:analogs & derivatives
D000975:Antioxidants; D016227:Benzoquinones; D005292:Ferricyanides; D016166:Free Radical Scavengers; D005994:Glycerophosphates; D017382:Reactive Oxygen Species; D013386:Succinates; C028325:ubiquinone Q3; D014451:Ubiquinone; C007931:hexacyanoferrate III; D006861:Hydrogen Peroxide; C036619:idebenone; C025203:Ubiquinone Q1