The role of CYP26 enzymes in retinoic acid clearance.
The role of CYP26 enzymes in retinoic acid clearance.
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DOI：
10.1517/17425250903032681
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发表时间：
2009-08
影响因子：
4.3
通讯作者：
Isoherranen N
中科院分区：
文献类型：
--
作者：
Thatcher JE;Isoherranen N
视黄酸 (RA) 是调节基因转录和细胞周期的关键信号分子。在过去的几十年里，对 RA 信号传导的了解急剧增加，但全身 RA 稳态与单个细胞基因调控之间的联系仍不清楚。有人提出，细胞色素 P450 家族 26 (CYP26) 酶通过灭活不需要 RA 的细胞中的 RA 来确定细胞对 RA 的暴露程度。 CYP26 酶已被证明可以有效地代谢 RA，并且在选定的系统中它们也可以被 RA 诱导。然而，它们在不同细胞类型中的表达模式以及对其功能的机制了解仍然缺乏。根据初步动力学数据和蛋白质表达水平，人们可以预测，如果 CYP26A1 在肝脏中表达，即使水平非常低，它也将成为该组织中的主要 RA 羟化酶。因此，当人们的目标是增加循环或细胞 RA 浓度时，它是药物开发中一个有吸引力的药理学靶点。为了进一步了解 CYP26 酶如何促进 RA 稳态的调节，需要 CYP26 的结构信息、市售重组酶以及良好的特异性和敏感性抗体。
Retinoic acid (RA) is a critical signaling molecule that regulates gene transcription and the cell cycle. Understanding of RA signaling has increased dramatically over the past decades, but the connection between whole body RA homeostasis and gene regulation in individual cells is still unclear. It has been proposed that cytochrome P450 family 26 (CYP26) enzymes have a role in determining the cellular exposure to RA by inactivating RA in cells that do not need RA. The CYP26 enzymes have been shown to metabolize RA efficiently and they are also inducible by RA in selected systems. However, their expression patterns in different cell types and a mechanistic understanding of their function is still lacking. Based on preliminary kinetic data and protein expression levels, one may predict that if CYP26A1 is expressed in the liver at even very low levels, it will be the major RA hydroxylase in this tissue. As such, it is an attractive pharmacological target for drug development when one aims to increase circulating or cellular RA concentrations. To further the understanding of how CYP26 enzymes contribute to the regulation of RA homeostasis, structural information of the CYP26’s, commercially available recombinant enzymes and good specific and sensitive antibodies are needed.
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1111/j.1365-2362.1984.tb02104.x
发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1080/14756360600742014
发表时间：
2006-08-01
影响因子：
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作者：
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通讯作者：
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