Tirumalai P S, Bhamre S, Upadhya S C, Boyd M R, Ravindranath V
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Biochem Pharmacol. 1998 Aug 1;56(3):371-5. doi: 10.1016/s0006-2952(98)00036-7.
Cytochrome P450 (P450) content and P450-mediated mono-oxygenase activities were measured in microsomes prepared from various regions of rat brain. The regional P450 content in brain varied between 0.1 and 0.15 nmol/mg of protein, with the brainstem and cerebellum showing the highest levels. NADPH cytochrome c reductase activity was highest in the cortex followed by cerebellum and brainstem as compared with the whole brain. Mono-oxygenase activities also varied among the various brain regions. Southern blot analysis of the cDNA synthesized from the poly(A)RNA isolated from rat brain regions and hybridized with cDNA to rat liver P4502B or P4502E1 revealed the presence of a transcript in untreated rat brain that had a molecular mass similar to that of the corresponding transcript from rat liver. Immunoblot analyses using antisera to purified rat liver P4502E1, P450(2B1/2B2), and a phenobarbital-inducible form of rat brain P450 revealed the presence of corresponding immunoreactive protein bands in all the brain regions examined. The present study demonstrated the diversity in the distribution of P450 and associated mono-oxygenase activities in brain and thus may reflect the differential capability of various regions of the brain to detoxify or bioactivate diverse xenobiotics.
在从大鼠脑的不同区域制备的微粒体中测定了细胞色素P450（P450）含量和P450介导的单加氧酶活性。脑中各区域的P450含量在0.1至0.15 nmol/mg蛋白质之间变化，其中脑干和小脑的含量最高。与全脑相比，NADPH细胞色素c还原酶活性在皮质中最高，其次是小脑和脑干。单加氧酶活性在不同脑区之间也有所不同。对从大鼠脑区分离的聚腺苷酸RNA（poly(A)RNA）合成的cDNA进行Southern印迹分析，并与大鼠肝脏P4502B或P4502E1的cDNA杂交，结果显示在未处理的大鼠脑中存在一种转录本，其分子量与大鼠肝脏相应转录本的分子量相似。使用针对纯化的大鼠肝脏P4502E1、P450(2B1/2B2)以及大鼠脑P450的苯巴比妥诱导形式的抗血清进行免疫印迹分析，结果显示在所有检测的脑区中均存在相应的免疫反应性蛋白条带。本研究证明了脑中P450及其相关单加氧酶活性分布的多样性，因此可能反映了脑的不同区域对多种异源生物进行解毒或生物活化的不同能力。
