Involvement of decreased glutamate receptor subunit GluR2 expression in lead-induced neuronal cell death
Involvement of decreased glutamate receptor subunit GluR2 expression in lead-induced neuronal cell death
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DOI：
10.2131/jts.38.513
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发表时间：
2013-06-01
影响因子：
2
通讯作者：
Ohta, Shigeru
中科院分区：
文献类型：
--
作者：
Ishida, Keishi;Kotake, Yaichiro;Ohta, Shigeru
已知铅可诱导神经毒性，特别是在幼儿中，而GluR 2（AMPA型谷氨酸受体亚单位）在神经元细胞存活中起重要作用。因此，我们假设，改变GluR 2的表达在铅诱导的神经元细胞死亡中发挥作用。为了验证这一想法，我们研究了暴露于5和20 μ M铅1-9天对原代培养的大鼠皮层神经元的活力和GluR 2表达的影响。5 μ M铅暴露9天或20 μ M铅暴露7-9天，台盼蓝染色细胞数增加，20 μ M铅暴露9天，LDH释放增加。GluR 2的表达降低暴露于5-100 μ M的铅，但不是0.1-1 μ M的铅，9天。免疫细胞化学也证实，在铅的存在下，GluR 2的表达下降。应用50 ng/ml脑源性神经营养因子（BDNF）导致铅诱导的神经元细胞死亡的恢复，伴随着GluR 2表达的增加。我们的研究结果表明，长期暴露于铅诱导神经元细胞死亡，与GluR 2的表达减少。
Lead is known to induce neurotoxicity, particularly in young children, and GluR2, an AMPA-type glutamate receptor subunit, plays an important role in neuronal cell survival. Therefore, we hypothesized that altered GluR2 expression plays a role in lead-induced neuronal cell death. To test this idea, we investigated the effect of exposure to 5 and 20 mu M lead for 1-9 days on the viability and GluR2 expression of primary-cultured rat cortical neurons. The number of trypan-blue stained cells was increased by exposure to 5 mu M lead for 9 days or 20 mu M lead for 7-9 days, and LDH release was increased after exposure to 20 mu M lead for 9 days. GluR2 expression was reduced by exposure to 5-100 mu M lead, but not 0.1-1 mu M lead, for 9 days. Immunocytochemistry also confirmed that GluR2 expression was decreased in the presence of lead. Application of 50 ng/ml brain-derived neurotrophic factor (BDNF) led to a recovery of lead-induced neuronal cell death, accompanied with increased GluR2 expression. Our results suggest that long-term exposure to lead induces neuronal cell death, in association with a decrease of GluR2 expression.