Acrolein is a mitochondrial toxin: effects on respiratory function and enzyme activities in isolated rat liver mitochondria.
Acrolein is an air pollutant from cigarette smoking and other pollutions and also a by-product of lipid peroxidation. Studies have demonstrated that acrolein causes cytotoxicity and genotoxicity, including liver damage and death of hepatocytes. However, the toxic effects and the underlying mechanisms of acrolein on mitochondria, especially, on liver mitochondria, have not been well studied. In the present study, we investigated the toxic effects and mechanisms of acrolein on mitochondria isolated from rat liver by examining mitochondrial respiration, dehydrogenases, complex I, II, III, IV and V, permeability transition, and protein oxidation. Acrolein incubation (10-1000 microM, or 0.02-2 micromol/mg protein) with mitochondria caused dose-dependent inhibition of NADH- and succinate-linked mitochondrial respiration chain, change of mitochondrial permeability transition, increase in protein carbonyls, and selective enzyme inhibition of mitochondrial complex I, II, pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, but no effects on mitochondrial complex III, IV, V and malate dehydrogenase. These results suggest that acrolein is a mitochondrial toxin and that mitochondrial dysfunction caused by acrolein may play an important role in acrolein toxicity such as hepatotoxicity and also smoking-related diseases.
Sun
Lijuan
L
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic China.
Luo
Cheng
C
Long
Jiangang
J
Wei
Dongzhi
D
Liu
Jiankang
J
D000171:Acrolein / Q000633:toxicity*; D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling / Q000187:drug effects; D015233:Models, Statistical; D051381:Rats; D017207:Rats, Sprague-Dawley; D013367:Submitochondrial Particles / Q000378:metabolism; D013997:Time Factors
D000393:Air Pollutants; D000171:Acrolein