Nakamura Kayo, Fujiki Takeshi, Tamura Hiro-omi
Kyoritsu University of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo 1-5-8512, Japan.
Exp Eye Res. 2005 Dec;81(6):710-5. doi: 10.1016/j.exer.2005.04.011. Epub 2005 Jun 20.
Previously we have reported our analyses of cytochrome P450 (CYP) expression in rat ocular tissues and in our current study we have extended these analyses to the different stages of growth in both male and female rats. Additionally, we have examined the expression levels of the different conjugation enzymes, sulfotransferases (SULTs), UDP-glucuronosyl transferases (UGTs) and glutathione S-transferases (GSTs), in ocular tissues. In 5-week-old animals, the CYP genes, CYP2B2 and CYP3A1, were abundantly expressed in the lens, with higher CYP1A1 expression detectable in the extra-lenticular tissues, of both genders. However, the expression of CYP1A2 and CYP2E1 in female ocular tissues was more extensive than in male. Moreover, in females the expression of the phenol-sulfating SULTs, ST1A1, ST1B1 and ST1C1, was more abundant in the extra-lenticular tissues, whereas the levels of the hydroxysteroid-sulfating SULTs, ST2A1 and ST2A5, predominated in the lens. The expression levels of the UGTs, UGT1A1, UGT1A6 and UGT2B1, were also higher in the female extra-lenticular tissues but the expression of the GSTA subfamily (GSTA1 and GSTA2) was very weak in the ocular tissues of both genders. The overall gene expression profiles were found to change with the age of the animals (from 3 to 8 weeks) and, in general, the expression levels of the CYPs and SULTs declined with age, whereas the levels of the UGTs and GSTs increased. These results demonstrate that the expression profiles of drug metabolising enzymes show both region- and gender-specific patterns in rat ocular tissues.
此前我们已报道了对大鼠眼部组织中细胞色素P450（CYP）表达的分析，在当前研究中，我们将这些分析扩展到了雄性和雌性大鼠生长的不同阶段。此外，我们还检测了眼部组织中不同结合酶，即磺基转移酶（SULTs）、尿苷二磷酸葡萄糖醛酸基转移酶（UGTs）和谷胱甘肽S-转移酶（GSTs）的表达水平。在5周龄的动物中，CYP基因CYP2B2和CYP3A1在晶状体中大量表达，在晶状体外组织中可检测到较高的CYP1A1表达，两性均如此。然而，CYP1A2和CYP2E1在雌性眼部组织中的表达比雄性更广泛。此外，在雌性中，酚类硫酸化SULTs，即ST1A1、ST1B1和ST1C1，在晶状体外组织中的表达更丰富，而羟基类固醇硫酸化SULTs，即ST2A1和ST2A5，则在晶状体中占主导地位。UGTs，即UGT1A1、UGT1A6和UGT2B1，在雌性晶状体外组织中的表达水平也更高，但GSTA亚家族（GSTA1和GSTA2）在两性的眼部组织中的表达非常弱。发现总体基因表达谱随动物年龄（从3周到8周）而变化，一般来说，CYPs和SULTs的表达水平随年龄下降，而UGTs和GSTs的水平则升高。这些结果表明，药物代谢酶的表达谱在大鼠眼部组织中呈现出区域和性别特异性模式。
