Species-specific expression of CYP4B1 in rabbit and human gastrointestinal tissues.

Species-specific expression of CYP4B1 in rabbit and human gastrointestinal tissues.
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CYP4B1 在兔和人胃肠道组织中的物种特异性表达。

DOI:
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发表时间:
1994
期刊:
Pharmacogenetics (London)
影响因子:
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通讯作者:
M. McManus
M. McManus
中科院分区:
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文献类型:
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作者:
R. McKinnon;W. Burgess;F. Gonzalez;R. Gasser;M. McManus

文献摘要

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CYP 4 B1是一种P450酶,显示组织和物种特异性调节。兔CYP 4 B1酶对前致癌芳香胺具有活性。在本研究中,CYP 4 B1表达的特点是在兔组织中使用组织学技术,北方印迹和Western印迹。尝试使用可用的人体组织进行类似的分析。CYP 4 B1 mRNA和蛋白在整个家兔小肠和结肠中均有表达。用CYP 4 B1特异性RNA探针在兔胃中检测到一个独特的1.8kb转录本,该转录本比在其他组织中发现的转录本小。在该组织中未检测到CYP 4 B1蛋白。在兔肝脏中,CYP 4 B1主要在1区肝细胞(门静脉周围)中被苯巴比妥诱导。在人体中,使用原位杂交证明CYP 4 B1在人结肠中的表达水平较低,但在肝脏或小肠中没有表达。除胃外,所有兔胃肠道组织均具有高活化2-氨基芴的能力,与CYP 4 B1表达相容。相反,在人胃肠道微粒体中未观察到活性。因此,本研究表明,CYP 4 B1是一个丰富的P450在兔胃肠道和识别CYP 4 B1的表达和功能的物种特异性差异。
CYP4B1 is a P450 enzyme displaying tissue and species specific regulation. The rabbit CYP4B1 enzyme exhibits activity towards procarcinogenic aromatic amines. In the present study, CYP4B1 expression has been characterized in rabbit tissues using histological techniques, Northern blotting and Western blotting. Similar analyses were attempted using available human tissues. CYP4B1 mRNA and protein was demonstrated throughout the rabbit small intestine and colon. A unique 1.8 kb transcript, that is smaller than the transcript found in other tissues, was detected in rabbit stomach with a CYP4B1 specific RNA probe. No CYP4B1 protein was detected in this tissue. In rabbit liver, CYP4B1 was induced by phenobarbital primarily in zone 1 hepatocytes (periportal). In humans, CYP4B1 expression was demonstrated at low levels in human colon using in situ hybridization but not in liver or the small intestine. All rabbit gastrointestinal tissues other than stomach possess a high capacity for the activation of 2-aminofluorene compatible with CYP4B1 expression. In contrast, no activity was observed in human gastrointestinal microsomes. The present study therefore shows that CYP4B1 is an abundant P450 in the rabbit gastrointestinal tract and identifies species-specific differences in CYP4B1 expression and function.