Involvement of mitochondrial pathway in benzo[a]pyrene-induced neuron apoptosis
Involvement of mitochondrial pathway in benzo[a]pyrene-induced neuron apoptosis
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DOI：
10.1177/0960327113493301
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发表时间：
2014-03
影响因子：
2.8
通讯作者：
J. Nie;Hongmei Zhang;Jie Zhao;Hui-Jun Liu;Qiao Niu
中科院分区：
文献类型：
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作者：
J. Nie;Hongmei Zhang;Jie Zhao;Hui-Jun Liu;Qiao Niu
苯并[a]芘（B[a]P）是一种广泛存在于环境中的致癌物质。虽然B[a]P的神经毒性作用尚未引起人们的广泛关注，但B[a]P对学习和记忆的毒性作用已有报道。由于众所周知神经元凋亡在许多刺激引发的学习和记忆障碍中起主要作用，因此已努力检查B[a] P诱导的神经毒性是否通过B2 O3介导的凋亡发生。本研究采用体外培养的新生大鼠脑神经元，观察B[a]P诱导的神经元凋亡。不同剂量的B[a]P与S9共同孵育40 h后，B[a] P处理的神经元凋亡率呈剂量依赖性增加。进一步分析表明，B[a] P诱导的细胞凋亡伴随着线粒体膜电位的丧失、细胞色素c从线粒体释放到胞质溶胶、抗凋亡蛋白B细胞淋巴瘤-2（Bcl-2）水平下调，同时促凋亡蛋白Bcl-2相关X蛋白（Bax）水平上调，以及半胱氨酸蛋白酶-9和-3的水平和活性增加。而B[a] P暴露组和对照组的caspase-8活性无明显差异。总之，这些结果表明，B[a]P上调Bax和下调Bcl-2在培养的大脑神经元中的表达，这导致线粒体释放细胞色素c，半胱氨酸蛋白酶3激活和神经元凋亡死亡。
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.