title: Involvement of mitochondrial pathway in benzo[a]pyrene-induced neuron apoptosis.
abstract: Benzo[a]pyrene (B[a]P), a well-known carcinogen, is widespread in the environment. Although the neurotoxic effect of B[a]P has not drawn much attention, toxic effects of B[a]P on learning and memory have been reported. Since it is well known that neuronal apoptosis plays a major role in impairment of learning and memory triggered by many stimuli, an effort has been made to examine whether the B[a]P-induced neurotoxicity occurs through mitochondria-mediated apoptosis. Cultured newborn rat cerebral neurons were used to clarify the apoptosis induced by B[a]P in the study. After incubating with different doses of B[a]P in presence of S9 for 40 h, the apoptotic rates of B[a]P-treated neurons increased in a dose-dependent manner. Further analysis showed that B[a]P-induced apoptosis was accompanied by loss of mitochondrial membrane potential, release of cytochrome c from mitochondria to the cytosol, downregulation of antiapoptotic protein B-cell lymphoma-2 (Bcl-2) levels with concurrent upregulation in proapoptotic Bcl-2-associated X protein (Bax) levels, and increase in the levels and activities of caspases-9 and -3. However, there was no difference in the activity of caspase-8 between B[a]P-exposed neurons and controls. Collectively, these results showed that B[a]P upregulates Bax and downregulates Bcl-2 expression in cultured cerebral neurons, which leads to mitochondrial release of cytochrome c, caspase-3 activation and neuronal apoptotic death.
authors.affiliation: 1Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China.
authors.forename: J-S
authors.initials: JS
authors.lastname: Nie
authors.forename: H-M
authors.initials: HM
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: H-J
authors.initials: HJ
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Niu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D061251:Primary Cell Culture; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014404:Tubulin / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D017304:Annexin A5; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D019253:Proto-Oncogene Proteins c-bcl-2; C488416:Tubb3 protein, rat; D014404:Tubulin; D051028:bcl-2-Associated X Protein; D001564:Benzo(a)pyrene; D045304:Cytochromes c; D020169:Caspases
keywords: Benzo[a]pyrene; apoptosis; mitochondria; neurotoxicity