Effects and neuro-toxic mechanisms of 2, 2′, 4, 4′, 5, 5′-hexachlorobiphenyl and endosulfan in neuronal stem cells
Effects and neuro-toxic mechanisms of 2, 2′, 4, 4′, 5, 5′-hexachlorobiphenyl and endosulfan in neuronal stem cells
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DOI：
10.1292/jvms.63.1183
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发表时间：
2001-11-01
影响因子：
1.2
通讯作者：
Lee, YS
中科院分区：
文献类型：
--
作者：
Kang, KS;Park, JE;Lee, YS
内分泌干扰物是外源性化合物，被认为可以模仿雌激素或其他激素的作用，影响体内的内分泌活动（Juberg, 2000）。这些化学物质不仅对生殖系统有不利影响，而且在发育和整个生命过程中对中枢神经系统也有不利影响。多氯联苯（PCBs）是一类环境持久性和广泛存在的卤代烃。据报道，多氯联苯是潜在的神经毒物。硫丹是一种有机氯杀虫剂，广泛用于控制蔬菜、棉花和水果中的害虫。为了确定2,2 ',4,4 ',5,5 '，六氯联苯（2,4,5 - hcb）和硫丹对胚胎神经系统的影响，我们从胚胎第17天的大鼠脑中分离神经干细胞。分离的神经干细胞表现出多能性。干细胞可以分化为神经元和神经胶质细胞。硫丹和2,4,5 - hcb处理的细胞中神经突的形成。与未经处理的细胞相比，它似乎有所减少。为了了解2,4,5 - hcb和硫丹对神经干细胞的神经毒性机制，我们研究了丝裂原激活的蛋白激酶活性（MAPK）和间隙连接细胞间通讯（GJIC）。硫丹降低MAPK活性呈剂量依赖性。与未处理的细胞相比，硫丹和2,4,5 - hcb通过刮载染料转移（SL/DT）抑制GJIC。2,4,5 - hcb和硫丹对连接蛋白43的表达呈剂量依赖性。这些结果表明，2,4,5 - hcb和硫丹可能抑制神经干细胞的分化和增殖以及在维持细胞稳态中起重要作用的间隙连接细胞间通讯。
Endocrine disrupters are exogenous compounds thought to mimic the action of estrogen or other hormones and influence endocrine activity in the body (Juberg, 2000). These chemicals have adverse effects not only in the reproductive system but also in the central nervous system during development and throughout life. Polychlorinated biphenyls (PCBs) are a class of environmentally persistent and widespread halogenated hydrocarbons. It has been reported that PCBs are potential neurotoxicants. Endosulfan is an organochlorine insecticide that is extensively used to control pests in vegetables, cotton, and fruits. To determine the effect of 2, 2', 4, 4' 5, 5', hexachlorobiphenyl(2, 4, 5-HCB) and endosulfan on embryo nervous system, we isolated neural stem cells from rat brain at embryonic day 17. Isolated neural stem cells showed pluripotenty. Stem cells could differentiate into neurons and glia. Neurite formation in endosulfan and 2, 4, 5-HCB treated cells. And it appeared to be decreased as compared with that in untreated cells. In order to know the neuro-toxic mechanisms of 2, 4, 5-HCB and endosulfan: in neuronal stem cells, we investigated mitogen-activated protein kinase activity (MAPK) and gap junctional intercellular communication (GJIC). Endosulfan decreased the MAPK activity in dose dependent manner. Endosulfan and 2, 4, 5-HCB inhibited GJIC compared to the untreated cell by scrape loading dye transfer (SL/DT). 2, 4, 5-HCB and endosulfan decreased the expression of connexin 43 in dose dependent manner. These results indicated that 2, 4, 5-HCB and endosulfan may inhibit differentiation and proliferation of neural stem cells and gap junctional intercellular communication which play a crucial role in the maintenance of cellular homeostasis.