Regulation of the induction of a cytochrome P-450 prostaglandin omega-hydroxylase by pregnancy in rabbit lung.
Regulation of the induction of a cytochrome P-450 prostaglandin omega-hydroxylase by pregnancy in rabbit lung.
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兔肺妊娠对细胞色素 P-450 前列腺素 omega-羟化酶诱导的调节。
DOI：
10.1073/pnas.84.22.7911
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发表时间：
1987
影响因子：
11.1
通讯作者：
Masters,BS
中科院分区：
文献类型：
--
作者：
Muerhoff,AS;Williams,DE;Leithauser,MT;Jackson,VE;Waterman,MR;Masters,BS
研究了妊娠期成年家兔细胞色素P-450，前列腺素（PG）ω-羟化酶（P-450 PG-ω）的诱导机制。这种P-450同工酶区域特异性地在碳-20（ω位置）羟基化PGE 1、PGA 1和PGF 2 α。与非妊娠兔相比，妊娠25- 28天兔肺中每分钟每mg微粒体蛋白形成0.07 nmol 20-OH-PGE 1至3.05 nmol 20-OH-PGE 1，可诱导该酶的比活性。免疫印迹研究与多克隆抗体提出了对这个P-450表明，有一个伴随的孕龄依赖性增加的P-450 PG-ω微粒体蛋白质的量伴随ω-羟化酶活性的增加。在产后3天内，ω-羟化酶活性和免疫可检测的P-450 PG-ω的量急剧下降至接近对照水平。在体外翻译的总细胞RNA，提取自妊娠兔的肺在整个妊娠期的不同天，和免疫沉淀的新合成的P-450 PG-ω证明了一个类似的孕龄依赖性增加的可翻译的P-450 PG-ω mRNA，与ω-羟化酶活性和P-450 PG-ω蛋白水平。这些数据表明，该P-450的诱导可能发生在转录水平，此外，在兔肺细胞色素P-450 PG-ω表达的控制在蛋白质和mRNA水平上受到严格调控。
The mechanism of induction of an adult rabbit cytochrome P-450, prostaglandin (PG) omega-hydroxylase (P-450PG-omega), during pregnancy has been investigated. This P-450 isozyme regiospecifically hydroxylates PGE1, PGA1, and PGF2 alpha at carbon-20 (the omega position). The specific activity of this enzyme is induced from 0.07 nmol of 20-OH-PGE1 to 3.05 nmol of 20-OH-PGE1 formed per min per mg of microsomal protein in the lungs of 25- to 28-day pregnant rabbits as compared to nonpregnant rabbits. Immunoblotting studies with a polyclonal antibody raised against this P-450 have shown that there is a concomitant gestational age-dependent increase in the amount of P-450PG-omega microsomal protein accompanying the increase of omega-hydroxylase activities. Within 3 days postpartum, both omega-hydroxylase activity and the amount of immunodetectable P-450PG-omega drop precipitously to near control levels. In vitro translation of total cellular RNA, extracted from the lungs of pregnant rabbits at various days throughout gestation, and immunoprecipitation of newly synthesized P-450PG-omega demonstrated a similar gestational age-dependent increase in translatable P-450PG-omega mRNA, as was observed with omega-hydroxylase activity and P-450PG-omega protein levels. These data suggest that the induction of this P-450 may occur at the transcriptional level and, furthermore, that control of cytochrome P-450PG-omega expression in the rabbit lung is tightly regulated at both protein and mRNA levels.