Lipopolysaccharide evokes the modulation of brain cytochrome P4501A in the rat
Lipopolysaccharide evokes the modulation of brain cytochrome P4501A in the rat
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DOI：
10.1016/s0006-8993(99)01773-4
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发表时间：
1999-09
期刊：
影响因子：
2.9
通讯作者：
K. Renton;Sandra Dibb;T. Levatte
中科院分区：
文献类型：
--
作者：
K. Renton;Sandra Dibb;T. Levatte
细胞色素P450酶系统是一个多基因酶家族，在全身炎症反应或感染期间在肝脏中受到调节。该酶的几种形式在脑的离散区域中表达，并可能在中枢神经系统（CNS）中药物和内源性化学物质的代谢中发挥关键作用。尽管大脑对炎症的反应与大多数组织不同，但我们研究了在局限于该器官的炎症期间大脑中主要细胞色素P450形式（CYP1A）的可能修饰。总脑CYP1A活性，乙氧基试卤灵脱烷基酶（EROD）测定，下调24和48小时后，单剂量的脂多糖（LPS）的管理。从区域上看，在皮层、海马和中脑中确定了类似的效果，但小脑的活动不受影响。使用针对CYP1A的抗体对冠状脑切片进行的检查表明，该酶分布在海马、丘脑和皮质的离散细胞中以及第三脑室周围的伸长细胞中。在这些区域中的每一个中，与盐水处理的动物相比，接受LPS的动物的免疫反应性降低。LPS还诱发整个大脑中小分子量热休克蛋白hsp27的表达，表明炎症反应的发生。这些研究表明，中枢神经系统的炎症导致脑中主要细胞色素P450形式的水平和活性发生变化。这可能对以炎症成分为特征的疾病状态期间CNS中药物和内源性化学物质的代谢或活化有影响。
The cytochrome P450 enzyme system is a multigene family of enzymes that is modulated in the liver during systemic inflammatory responses or during infection Several forms of the enzyme are expressed in discrete areas of the brain and likely play a critical role in the metabolism of drugs and endogenous chemicals in the central nervous system (CNS). Even though the brain responds to inflammation in a manner different from most tissues, we examined the possible modification of a major cytochrome P450 form (CYP1A) in the brain during inflammation confined to that organ. Total brain CYP1A activity, as measured by ethoxyresorufin dealkylase (EROD), was downregulated 24 and 48 h following the administration of a single dose of lipopolysaccharide (LPS). Regionally, a similar effect was determined in the cortex, hippocampus and the mid-brain but the activity in the cerebellum was unaffected. The examination of coronal brain sections using an antibody directed against CYP1A indicated that the enzyme was distributed in discrete cells of the hippocampus, thalamus and cortex and in the tanycytes surrounding the third ventricle. In each of these areas, the immunoreactivity was diminished in animals receiving LPS as compared to saline-treated animals. LPS also evoked the expression of the small molecular weight heat shock protein hsp27 throughout the brain indicating the development of an inflammatory response. These studies indicate that inflammation localized to the CNS causes an alteration in the levels and activity of a major cytochrome P450 form in the brain. This could have implications to the metabolism or activation of drugs and endogenous chemicals in the CNS during a disease state that features an inflammatory component.