Effect of methyl methacrylate on mitochondrial function and structure.
1. Treatment of isolated rat liver mitochondria with methyl methacrylate (MM) produced membrane disruption as evidenced by the release of citrate synthase, and changes in the ultrastructure of mitochondria. 2. At concentration 0.1%, MM uncoupled oxidative phosphorylation as evidenced by stimulation of state 4 respiration supported either by pyruvate plus malate or succinate (+rotenone) and ATP-ase activity in intact mitochondria. 3. At concentration 1% MM stimulated ATP-ase activity in intact mitochondria and succinate (+ rotenone) oxidation at state 4 and was without effect on this substrate oxidation at state 3. 4. MM inhibited pyruvate plus malate oxidation either at state 3 or in the presence of uncoupling agents. 5. MM inhibited the NADH oxidase of electron transport particles at a concentration which failed to inhibit either succinic oxidase or the NADH-ferricyanide reductase activity. 6. The data presented suggest that in the isolated mitochondria MM inhibits NADH oxidation in the vicinity of the rotenone sensitive site of complex I. 7. The general conclusion is that MM may block an electron transport and to uncouple oxidative phosphorylation in rat liver mitochondria. The overall in vitro effect would be to prevent ATP synthesis which could result in cell death under in vivo conditions.
Bereznowski
Z
Z
Department of Prosthetic Dentistry, Academic Medical School in Gdański, Poland.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003102:Colloids; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D008293:Malates / Q000737:chemistry / Q000378:metabolism; D020366:Methylmethacrylate; D008768:Methylmethacrylates / Q000633:toxicity*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000737:chemistry / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D012402:Rotenone / Q000737:chemistry / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013386:Succinates / Q000737:chemistry / Q000378:metabolism; D019802:Succinic Acid
D003102:Colloids; D008293:Malates; D008768:Methylmethacrylates; D009097:Multienzyme Complexes; D011773:Pyruvates; D013386:Succinates; D012402:Rotenone; D020366:Methylmethacrylate; C030298:malic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D019802:Succinic Acid; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C014227:ferricyanide reductase; D002950:Citrate (si)-Synthase; D000251:Adenosine Triphosphatases