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The modification of apoptosis correlated gene, protein and protein activity in rat hippocampus induced by benzoa pyrene sub-chronic exposure / 中华劳动卫生职业病杂志
Chinese Journal of Industrial Hygiene and Occupational Diseases ; (12): 195-200, 2013.
Article Dans Chinois | WPRIM | ID: wpr-343685
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of subchronic exposure to benzo[a]pyrene (B[a]P) on the mRNA and protein expression levels of apoptosis-related genes (bax, bcl-2, caspase-3, caspase-6, and caspase-9) and the activities of Caspase-3, Caspase-6, and Caspase-9 in the hippocampal neurons of rats and to investigate the neurotoxic mechanism by which B[a]P induces the apoptosis of neurons.</p><p><b>METHODS</b>Fifty-two healthy SD rat were randomly divided into five groups according to preliminary neurobehavioral test

results:

blank control group, solvent control group, and 1.0, 2.5, and 6.25 mg/kg B[a]P exposure groups; the rats in exposure groups were intraperitoneally injected with B[a]P every other day for 90 days. The Morris water maze was used to test the learning and memory ability of rats; flow cytometry was used to measure the apoptosis ratio of hippocampal neurons; real-time quantitative PCR and Western blot were used to measure the mRNA and protein expression levels of apoptosis-related genes; spectrophotometry was used to measure the activities of their en-coded proteins.</p><p><b>RESULTS</b>Compared with the blank control group, solvent control group, and 1.0 mg/kg B[a]P exposure group, the 2.5 and 6.25 mg/kg B[a]P exposure groups hada significantly longer mean escape latency period (P < 0.05) and a significantly increased number of times of platform crossing (P < 0.05), and the 6.25 mg/kg B[a]P exposure group had significantly lower length and percentage of time spent in the platform quadrant (P < 0.05). The early apoptosis ratio rose as the dose of B[a]P increased (P trend < 0.05); the early apoptosis ratios of 1.0, 2.5, and 6.25 mg/kg B[a]P exposure groups were significantly higher than those of blank control group and solvent control group (P < 0.05). Compared with the blank control group, solvent control group, and 1.0 and 2.5 mg/kg B[a]P exposure groups, the 6.25 mg/kg B[a]P exposure group had significantly increased Bax expression (P < 0.05) and significantly decreased Bcl-2 expression and Bcl-2/Bax ratio (P < 0.05). The 2.5 and 6.25 mg/kg B[a]P exposure groups had significantly higher expression levels of Caspase-3 and Caspase-6 than the blank control group, solvent control group, and 1.0 mg/kg B[a]P exposure group (P < 0.05). The activities of Caspase-3, Caspase-6, and Caspase-9 were significantly higher in the 2.5 and 6.25 mg/kg B[a]P exposure groups than in the blank control group and solvent control group (P < 0.05). There was a positive correlation between the activities of Caspase-3, Caspase-6, and Caspase-9 and early apoptosis ratio of hippocampal neurons in rats (r = 0.793, P = 0.019; r = 0.886, P = 0.006; r = 0.773, P = 0.025). There were no significant differences in the mRNA expression of Bax, Bcl-2, Caspase-3, Caspase-6, and Caspase-9 among these groups (P > 0.05).</p><p><b>CONCLUSION</b>Subchronic exposure to B[a]P can induce apoptosis of hippocampal neurons; its mechanism may be related to the fact that B[a]P can induce upregulated expression of Bax, inhibit expression of Bcl-2, lead to decrease in Bcl-2/Bax ratio, induce upregulated expression of Caspase-3 and Caspase-6, and cause increase in the activities of Caspase-3, Caspase-6, and Caspase-9.</p>
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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Anatomopathologie / Benzo[a]pyrène / Rat Sprague-Dawley / Apoptose / Protéines proto-oncogènes c-bcl-2 / Caspases / Biologie cellulaire / Protéine Bax / Toxicité / Hippocampe Limites du sujet: Animaux langue: Chinois Texte intégral: Chinese Journal of Industrial Hygiene and Occupational Diseases Année: 2013 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Anatomopathologie / Benzo[a]pyrène / Rat Sprague-Dawley / Apoptose / Protéines proto-oncogènes c-bcl-2 / Caspases / Biologie cellulaire / Protéine Bax / Toxicité / Hippocampe Limites du sujet: Animaux langue: Chinois Texte intégral: Chinese Journal of Industrial Hygiene and Occupational Diseases Année: 2013 Type: Article