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底鳉胚胎发育期间微粒体电子传递和异生素单加氧酶活性

Microsomal electron transport and xenobiotic monooxygenase activities during the embryonic period of development in the killifish, Fundulus heteroclitus.

作者信息

Binder R L, Stegeman J J

出版信息

Toxicol Appl Pharmacol. 1984 May;73(3):432-43. doi: 10.1016/0041-008x(84)90096-6.

Abstract

The developmental patterns of aryl hydrocarbon hydroxylase (AHH) activity and NADPH-cytochrome c reductase activity were followed during embryonic development in Fundulus. AHH activity was localized in microsomal fractions prepared from whole Fundulus embryos and eleutheroembryos. On the basis of this subcellular localization, the requirements of O2 and NADPH for activity, and sensitivity to carbon monoxide and cytochrome c inhibition, the AHH activity in Fundulus embryos and eleutheroembryos appeared to be cytochrome P-450 dependent. AHH activity was measurable in stages prior to the appearance of the liver rudiment, and during subsequent embryonic development the extrahepatic tissues were likely to have contributed substantially to the AHH activity measured. At all stages assayed before hatching, microsomal AHH specific activity remained uniformly low, but within 24 hr of hatching, AHH specific activity increased about ninefold. This posthatching increase in AHH activity was not age dependent, nor developmental stage dependent, but rather required hatching, and was not due to the presence of endogenous inhibitors in prehatching stages. The levels of NADPH-cytochrome c reductase activity and AHH activity were not closely correlated in whole embryo and eleutheroembryo microsomes, but the AHH activity in these preparations apparently was not limited by the levels of the NADPH-cytochrome c (P-450) reductase. The presence of AHH activity in Fundulus embryos during the period of active organogenesis, prior to hatching, indicates that this species is likely to be susceptible to a variety of teratogens requiring metabolic activation, and this may be the case for other species of fish as well.

摘要

在底鳉胚胎发育过程中,对芳烃羟化酶(AHH)活性和NADPH-细胞色素c还原酶活性的发育模式进行了跟踪研究。AHH活性定位于从整个底鳉胚胎和幼胚制备的微粒体部分。基于这种亚细胞定位、活性对氧气和NADPH的需求以及对一氧化碳和细胞色素c抑制的敏感性,底鳉胚胎和幼胚中的AHH活性似乎依赖于细胞色素P-450。在肝脏原基出现之前的阶段就能检测到AHH活性,在随后的胚胎发育过程中,肝外组织可能对所测得的AHH活性有很大贡献。在孵化前测定的所有阶段,微粒体AHH比活性一直保持在较低水平,但在孵化后24小时内,AHH比活性增加了约9倍。孵化后AHH活性的这种增加与年龄无关,也与发育阶段无关,而是需要孵化,并且不是由于孵化前阶段存在内源性抑制剂所致。在整个胚胎和幼胚微粒体中,NADPH-细胞色素c还原酶活性水平与AHH活性水平没有密切相关性,但这些制剂中的AHH活性显然不受NADPH-细胞色素c(P-450)还原酶水平的限制。在孵化前活跃器官发生期,底鳉胚胎中存在AHH活性,这表明该物种可能易受多种需要代谢激活的致畸剂影响,其他鱼类物种可能也是如此

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