Disruption of Retinoic Acid Receptor Signaling by Environmental Pollutants
Disruption of Retinoic Acid Receptor Signaling by Environmental Pollutants
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DOI：
10.1248/jhs.56.221
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发表时间：
2010
影响因子：
--
通讯作者：
D. Inoue;K. Sei;M. Ike
中科院分区：
文献类型：
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作者：
D. Inoue;K. Sei;M. Ike
视黄酸（RA）受体（RAR）是响应于内源性RA（即，全反式RA和9-顺式RA。另一方面，众所周知，RA和相关类维生素A的缺乏和过量均可对发育中的脊椎动物胚胎造成多种致畸作用，这已被证明是RAR介导的过程。因此，干扰RAR并破坏RAR信号传导的异生物质环境污染物的出现（即，显示RAR激动或拮抗作用）可能对野生动物和人类的健康构成威胁。本文主要对RAR受体激动剂进行综述。我们总结了RAR激动剂活性的天然和外源性化合物确定使用体外生物测定系统和目前最近的实地研究表明RAR激动剂污染的发生在北美，中国和日本的水环境。RAR受体激动剂对环境的污染是最近发现的一个新的内分泌干扰问题，相关知识非常有限。需要进一步研究以获得准确的信息，以评估RAR激动剂在环境中的可能风险。
Retinoic acid (RA) receptors (RARs) are nuclear receptors that play a critical role in regulating cellular proliferation, development and differentiation in vertebrates in response to endogenous RAs, i.e., all-trans RA and 9-cis RA. On the other hand, it has been well-known that both a deficiency and an excess of RA and related retinoids can cause a variety of teratogenic effects on developing embryos of vertebrates, which has been proven to be an RAR-mediated process. Therefore, the occurrence of xenobiotic environmental pollutants that interfere with RARs and disrupt the RAR signaling (i.e., show RAR agonistic or antagonistic effects) may pose a threat to the health of wild animals and humans. This review mainly focuses on RAR agonists. We summarize the RAR agonistic activity of natural and xenobiotic compounds determined using in vitro bioassay systems and present recent field research showing the occurrence of RAR agonist contamination in the aquatic environment in North America, China and Japan. Environmental pollution by RAR agonists is a new endocrine disruption issue discovered very recently, and relevant knowledge is very limited. Further research will be required to obtain accurate information to assess the possible risks of RAR agonists in the environment.