Tsukahara Shinji, Yamamoto Shoji, Ahmed Sohel, Kunugita Naoki, Arashidani Keiichi, Fujimaki Hidekazu
National Institute for Environmental Studies, Tsukuba, Japan.
Neuroimmunomodulation. 2006;13(2):63-8. doi: 10.1159/000094829. Epub 2006 Jul 28.
A recent study from our research group showed that repeated exposure to low-level formaldehyde (FA) increases the production of nerve growth factor, involving the survival and maintenance of neurons, in the hippocampus of immunized mice. In the present study, we examined the effects of FA on apoptotic mechanisms regulating survival and death of cells and on N-methyl-D-aspartate (NMDA) receptors related to hippocampal functions in the mouse hippocampus.
Western blot analyses were performed for Bcl-2, Bax and NMDA receptor subtypes 2A and 2B of the hippocampus taken from C3H mice exposed to 0 or 400 ppb of FA with or without ovalbumin (OVA) immunization. Immunohistochemical analysis for active caspase-3 was also carried out for these mice.
The ratio of Bcl-2 to Bax expression levels significantly increased with 400-ppb FA exposure in OVA-immunized mice but not in mice without OVA immunization, although differences in each protein level were not significant among groups. Active caspase- 3-immunoreactive cells were found in the hippocampus. However, the number was only a few and not significantly affected by FA exposure and OVA immunization. NMDA receptor type 2A and 2B expression levels of FA-exposed mice were sustained at comparative levels with those for the control mice with or without OVA immunization.
These results indicate that changes in the Bcl-2/Bax expression ratio, which occurs with low-level FA exposure and immunization and may follow enhancement of nerve growth factor production, exerts a protective effect against cell death by apoptosis.
我们研究小组最近的一项研究表明,反复暴露于低水平甲醛(FA)会增加免疫小鼠海马体中神经生长因子的产生,这涉及神经元的存活和维持。在本研究中,我们研究了FA对调节细胞存活和死亡的凋亡机制以及对与小鼠海马体功能相关的N-甲基-D-天冬氨酸(NMDA)受体的影响。
对暴露于0或400 ppb FA且有或无卵清蛋白(OVA)免疫的C3H小鼠的海马体进行Bcl-2、Bax以及NMDA受体亚型2A和2B的蛋白质免疫印迹分析。还对这些小鼠进行了活性半胱天冬酶-3的免疫组织化学分析。
在OVA免疫的小鼠中,暴露于400 ppb FA会使Bcl-2与Bax表达水平的比值显著增加,但在未进行OVA免疫的小鼠中则不会,尽管各组中每种蛋白质水平的差异并不显著。在海马体中发现了活性半胱天冬酶-3免疫反应性细胞。然而,数量很少,且不受FA暴露和OVA免疫的显著影响。暴露于FA的小鼠的NMDA受体2A和2B表达水平与有或无OVA免疫的对照小鼠的水平保持在相当水平。
这些结果表明,低水平FA暴露和免疫时发生的Bcl-2/Bax表达比值变化,可能伴随着神经生长因子产生的增强,对细胞凋亡引起的细胞死亡具有保护作用。