AGE-DEPENDENT EXPRESSION OF CYTOCHROME-P-450S IN RAT-LIVER
AGE-DEPENDENT EXPRESSION OF CYTOCHROME-P-450S IN RAT-LIVER
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DOI：
10.1016/0925-4439(91)90034-7
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发表时间：
1991-10-21
期刊：
影响因子：
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通讯作者：
FUNAE, Y
中科院分区：
文献类型：
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作者：
IMAOKA, S;FUJITA, S;FUNAE, Y
本文研究了1周龄至104周龄(24个月)不同月龄雄性和雌性大鼠肝微粒体多种形式细胞色素P-450水平和睾酮羟化活性的增龄变化。用分光光度法测得的细胞色素P-450总量在雌雄大鼠中随年龄变化不大。雄性大鼠的睾酮2-α、2-β、6-β、15-α、16-α和16-β羟化活性显著高于雌性大鼠，且是发育诱导的。雄性大鼠的这些活性随着年龄的增长而下降，到104周龄时雌性大鼠的这些活性下降到非常低的水平。睾酮7-α羟化活性在3周龄时达到最大值，无论性别。免疫印迹法检测单个细胞色素P-450的表达水平。P450IA1和IA2(3-甲基胆菲诱导型)和P450IIB1和IIB2(苯巴比妥诱导型)在所有年龄段的雌雄大鼠中都有低水平的检测。P450IIA2、IIC11和IVA2仅在雄性大鼠中检测到，并诱导其发育。这些雄性特有的形式在104周龄的雄性大鼠肝脏中消失。P450IIC12是一种典型的雌性特有形式，在雌性大鼠发育中被诱导，在3周龄和104周龄的雄性大鼠中也被检测到。P450IIIA2(睾酮6-β-羟基酶)在雄性大鼠发育过程中被诱导，但在104周龄时消失。在雌性大鼠中，仅在1周龄和3周龄时检测到P450 IIIA2。P450IIA1、IIC6、IIE1和IVA3在任何年龄段的雌雄大鼠中均有表达。P450IIC6和IVA3是在发育过程中诱导的，并且在两性大鼠中检测到相似的水平。P450IIA1的表达水平在3周龄时最高，雌雄不限。与本研究中使用的其他细胞色素P-450相比，P450IIE1在衰老过程中的水平变化较小。这些观察为我们先前的假设提供了具体的证据，即雄性大鼠细胞色素P-450的每一种形式随着年龄的增长而以不同的模式改变，导致所有细胞色素P-450组成在老年时实际上是女性化的。
Age-related changes in the levels of multiple forms of cytochrome P-450 as well as in the testosterone hydroxylation activities of hepatic microsomes of male and female rats of different ages from 1 week to 104 weeks (24 months) were investigated. The total cytochrome P-450 measured photometrically did not change much with age in either male and female rats. Testosterone 2-alpha-, 2-beta-, 6-beta-, 15-alpha-, 16-alpha- and 16-beta-hydroxylation activities of male rats were much higher than those in female rats and were induced developmentally. These activities in male rats declined with aging to the very low level in female rats by 104 weeks of age. Testosterone 7-alpha-hydroxylation activity was maximum at 3 weeks of age in rats of both sexes. The levels of individual cytochrome P-450s were measured by immunoblotting. P450IA1 and IA2 (3-methylcholanthrene-inducible forms) and P450IIB1 and IIB2 (phenobarbital-inducible forms) were detected at low levels in rats of both sexes at all ages. P450IIA2, IIC11 and IVA2 were detected in male rats only and were induced developmentally. These male-specific forms disappeared in male rat liver at 104 weeks of age. P450IIC12, a typical female-specific form, was induced developmentally in female rats and was also detected in male rats at 3 and 104 weeks of age. P450IIIA2 (testosterone 6-beta-hydroxylase) was induced developmentally in male rats, but disappeared when the rats were 104 weeks of age. In female rats, P450IIIA2 was detected only at 1 and 3 weeks of age. P450IIA1, IIC6, IIE1 and IVA3 were detected in rats of both sexes at any age. P450IIC6 and IVA3 were induced developmentally and detected at a similar level in rats of both sexes. The level of P450IIA1 was maximum at 3 weeks of age in rats of both sexes. The changes in the level of P450IIE1 during aging were small compared with the changes in other cytochrome P-450s used in this study. These observations provide concrete evidence to our earlier hypothesis that each of the forms of cytochrome P-450 in male rats alter with aging in different patterns resulting in a practical feminization of over-all cytochrome P-450 composition at old age.