Effect of the plasticizer di-(2-ethylhexyl)phthalate on oxidative phosphorylation in rat liver mitochondria: modification of the function of the adenine nucleotide translocator.
The effect of di-(2-ethylhexyl)phthalate (DEHP) on oxidative phosphorylation of isolated rat liver mitochondria was investigated. DEHP at concentrations of 20-1000 microM had no effect on state 4 respiration, but at 40 microM, DEHP decreased the rate of state 3 respiration by about 20%. Although DEHP had no effect on electron transport through the respiratory chain, it decreased the rate of adenosine triphosphate (ATP) synthesis. Its inhibition of ATP synthesis showed a similar concentration dependence to that of state 3 respiration. Furthermore, DEHP at 40 microM inhibited the uptake of [3H]adenosine diphosphate into mitochondria. DEHP also retarded the action of cationic uncoupling agents, which are known to modify the 29000-dalton protein involved in adenine nucleotide exchange. These results suggest that DEHP affects the activity of adenine nucleotide exchange and consequently partially decreases the rate of state 3 respiration. The action of DEHP on the 29000-dalton protein involves a protective effect against mitochondrial damage induced by hydrophobic cations or heavy metal cations.
Kora
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S
Technical R & D Division, Terumo Corp., Fuji, Japan.
Sado
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M
Terada
H
H
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010795:Phthalic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010795:Phthalic Acids; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D004051:Diethylhexyl Phthalate; D009713:Nucleotidyltransferases