Localization of cytochrome P-450 gene expression in normal and diseased human liver by in situ hybridization of wax-embedded archival material
✍ Scribed by Colin N. A. Palmer; Philip J. Coates; Susan E. Davies; Elizabeth A. Shephard; Ian R. Phillips
- Book ID
- 102849846
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 1004 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
The localization of the expression of several cytochrome P-450 genes in normal and diseased human liver was investigated by in s i t u hybridization of formalin-fixed, paraffin wax-embedded archival tissue samples with ssS-labeled antisense RNA probes. The results demonstrated that genes coding for members of the cytochrome P-450 3A subfamily (CYP3A) were preferentially expressed in hepatocytes in acinar zone 3 (the centrilobular region), whereas genes coding for CYP1A2, cyP2A, 2B and 2C were expressed uniformly throughout the liver acinus. In cirrhotic livers, CYP2A and 2B genes (and to a lesser extent, CYP3A genes) were highly expressed in isolated hepatocytes located at the junction of parenchyma with fibrous septa. The cause and significance of the position-dependent expression of specific cytochrome P-460 genes in normal and diseased human liver are discussed. (HEPATOLOGY 1992;16682-687.)
Cytochromes P-450 constitute a superfamily of hemoproteins that are of fundamental importance in normal liver function (1-3). They have been classified, on the basis of amino acid sequence homology into families (designated by Arabic numerals, e.g., CYP1, CYP2) and subfamilies (designated by capital letters, e.g., CYPBA, 2B) (4, 5). In a given species, members of different cytochrome P-450 families have less than 35% sequence similarity, whereas those of different subfamilies have between 35% and 65% identity. Individual components of a subfamily have more than 65% identity and are distinguished by Arabic numerals (e.g., CYP2A1, 2A2). To date, more than 25 distinct cytochromes P-450 have been identified in man (5).