Tripathi Vinay Kumar, Kumar Vivek, Singh Abhishek Kumar, Kashyap Mahendra Pratap, Jahan Sadaf, Kumar Dipak, Lohani Mohtashim
CSIR-Indian Institute of Toxicology Research, Integral University, Lucknow, Uttar Pradesh, India ; Department of Biotechnology, Integral University, Lucknow, Uttar Pradesh, India.
Toxicol Int. 2013 May;20(2):177-85. doi: 10.4103/0971-6580.117264.
Inducible expressions cytochrome P450s (CYPs) against environmental chemicals in brain tissues of experimental animals is well-documented. However, the precise role of specific brain cell type in the metabolism of different class of xenobiotics has not been explored adequately. We study the expression of selected CYPs (1A1/1A2, 2B1/2B2, 2E1) in primary cultures of rat brain neuronal and glial cell exposed to an organophosphate pesticide-monocrotophos (MCP), a known neurotoxicant. The cultured neurons and glial cells express significant expression of CYP1A1, 2B2 and 2E1 isoenzymes, where the levels were comparatively higher in neuronal cells. Neuronal cells exhibited greater induction of CYP2E1 against MCP exposure, while glial cells were having more vulnerability for CYP1A and 2B isoenzymes. Similarly, cells were showing substrate specific responses against the specific inducers of CYPs, that is, ethanol (2E1), cyclophosphamide (2B1/2B2), 3-methylcholanthrene (1A1/1A2). The altered expression and activity of selected CYPs in cultured neuronal and glial cells could be helpful in explaining the association between MCP-induced neurotoxicity/metabolism and synthesis or transport of the neurotransmitters. The induction of CYPs in glial cells may also have significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The differential expression pattern of CYPs in neuronal and glial cells exposed to MCP also indicate the selective sensitivity of these cells against the xenobiotics, hence suggested their suitability as tool to screen neurotoxicity potential of variety of xenobiotics.
实验动物脑组织中针对环境化学物质的细胞色素P450(CYPs)的诱导表达已有充分记录。然而,特定脑细胞类型在不同种类外源性物质代谢中的精确作用尚未得到充分探索。我们研究了暴露于有机磷农药久效磷(一种已知的神经毒物)的大鼠脑神经元和神经胶质细胞原代培养物中选定的CYPs(1A1/1A2、2B1/2B2、2E1)的表达。培养的神经元和神经胶质细胞表达了显著的CYP1A1、2B2和2E1同工酶,其中神经元细胞中的水平相对较高。神经元细胞对久效磷暴露表现出更大的CYP2E1诱导,而神经胶质细胞对CYP1A和2B同工酶更敏感。同样,细胞对CYPs的特定诱导剂表现出底物特异性反应,即乙醇(2E1)、环磷酰胺(2B1/2B2)、3-甲基胆蒽(1A1/1A2)。培养的神经元和神经胶质细胞中选定CYPs的表达和活性改变可能有助于解释久效磷诱导的神经毒性/代谢与神经递质合成或转运之间的关联。神经胶质细胞中CYPs的诱导也可能具有重要意义,因为这些细胞被认为参与保护神经元免受环境损伤并使其免受毒性。暴露于久效磷的神经元和神经胶质细胞中CYPs的差异表达模式也表明这些细胞对外源性物质具有选择性敏感性,因此表明它们适合作为筛选各种外源性物质神经毒性潜力的工具。