Styrene 7,8-oxide induces mitochondrial damage and oxidative stress in neurons.
Styrene 7,8-oxide (SO) is the main metabolite of styrene, a neurotoxic compound used industrially. Neurons exposed to SO undergo apoptosis with characteristic features including chromatin rearrangements and caspase activation. We report that the execution phase of apoptosis induced by SO (0.3 mM) in SK-N-MC neurons is triggered by translocation of apoptogenic factors (e.g., cytochrome c) into the cytosol. In addition, mitochondria exhibit lower Ca2+ capacity and loss of mitochondrial membrane potential (DeltaPsi). Lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS), is increased after 12 h. Pre-treatment with the antioxidant MnTBAP (100 microM) prevents the decrease of Ca2+ capacity, cytochrome c release, activation of caspases, exposure of phosphatidylserine and cell death. Hence, the neurotoxic effects of SO are related to mitochondrial damage and oxidative stress.
Institute of Environmental Medicine, Division of Toxicology and Neurotoxicology, Karolinska Institutet, Box 210, S-171 77 Stockholm, Sweden. elisabetta.dare@imm.ki.se
E
E
Daré
R
R
Tofighi
L
L
Nutt
M V
MV
Vettori
M
M
Emgård
A
A
Mutti
S
S
Ceccatelli
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism*; D004852:Epoxy Compounds / Q000633:toxicity*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004852:Epoxy Compounds; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D045304:Cytochromes c; C013690:styrene oxide; D002118:Calcium