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双酚 A 的急性作用:信号通路对未成年大鼠睾丸内钙离子内流的影响。

Acute effect of bisphenol A: Signaling pathways on calcium influx in immature rat testes.

机构信息

Laboratório de Hormônios & Transdução de Sinais, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil; UNOCHAPECÓ, Brazil; Normandie Univ, France; UNICAEN, Laboratoire Estrogènes, Reproduction, Cancer, CAEN cedex 5, France.

UNOCHAPECÓ, Brazil.

出版信息

Reprod Toxicol. 2018 Apr;77:94-102. doi: 10.1016/j.reprotox.2018.02.009. Epub 2018 Feb 21.

DOI:10.1016/j.reprotox.2018.02.009
PMID:29476780
Abstract

We investigated the acute effect of low concentrations of BPA on calcium influx and the mechanism of action of BPA in this rapid response in the rat testis. BPA increased calcium influx at 1 pM and 1 nM at 300 s of incubation, in a similar manner to that of estradiol. At 1 pM, BPA stimulated calcium influx independently of classical estrogen receptors, consistent with a G-protein coupled receptor. This effect also involves the modulation of ionic channels, such as K, TRPV1 and Cl channels. Furthermore, BPA is able to modulate calcium from intracellular storages by inhibiting SERCA and activating IP receptor/Ca channels at the endoplasmic reticulum and activate kinase proteins, such as PKA and PKC. The rapid responses of BPA on calcium influx could, in turn, trigger a cross talk by MEK and p38 activation and also mediate genomic responses.

摘要

我们研究了低浓度 BPA 对钙内流的急性影响,以及 BPA 在大鼠睾丸快速反应中的作用机制。BPA 在孵育 300 秒时,在 1 pM 和 1 nM 时增加钙内流,其方式与雌二醇相似。在 1 pM 时,BPA 刺激钙内流不依赖于经典雌激素受体,与 G 蛋白偶联受体一致。这种作用还涉及离子通道的调制,如 K、TRPV1 和 Cl 通道。此外,BPA 能够通过抑制 SERCA 和激活内质网中的 IP 受体/Ca 通道来调节细胞内储存的钙,并激活蛋白激酶,如 PKA 和 PKC。BPA 对钙内流的快速反应反过来又可以通过 MEK 和 p38 的激活引发细胞间通讯,并介导基因组反应。

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