Mol Pharmacol:研究人员发现双酚A对钙离子通道的不利影响

2013-05-06 Beyond 生物谷

许多人工合成产品中发现的一种物质双酚A被认为是有害的,特别是对胎儿和婴儿。波恩大学研究人员在实验中已经表明这种环境化学物质能阻断人类和小鼠的组织细胞膜上的钙离子通道。研究结果发表在Molecular Pharmacology杂志上。 工业化学品双酚A(BPA)是全世界广泛用于制造聚碳酸酯树脂和合成树脂的材料。这种物质已被证明会影响内分泌系统,对酶和载体蛋白的功能可能产生负面影响。 BPA与心脏

许多人工合成产品中发现的一种物质双酚A被认为是有害的,特别是对胎儿和婴儿。波恩大学研究人员在实验中已经表明这种环境化学物质能阻断人类和小鼠的组织细胞膜上的钙离子通道。研究结果发表在Molecular Pharmacology杂志上。

工业化学品双酚A(BPA)是全世界广泛用于制造聚碳酸酯树脂和合成树脂的材料。这种物质已被证明会影响内分泌系统,对酶和载体蛋白的功能可能产生负面影响。

BPA与心脏病,糖尿病,肥胖,癌症和神经功能障碍相关。胎儿和新生儿对BPA特别敏感。由于其不可预测的影响,2011年欧盟委员会婴儿奶瓶禁止使用BPA。

研究人员现在报告说,双酚A阻断多个必需的钙离子通道,BPA能可逆性地阻断小鼠和人类细胞的钙通道。

钙离子流经这些孔状的蛋白通道进入活细胞,例如控制心脏肌肉细胞,酶的活性以及​​神经细胞的收缩。新研究表明,BPA的确可以对人体健康产生不利影响。由于双酚A是可逆的结合钙通道,研究人员相信该物质至少有从体内被清楚的可能性。

doi:10.1124/mol.112.081372
PMC:
PMID:

Bisphenol A Inhibits Voltage-activated Ca2+ channels In Vitro: Mechanisms and Structural Requirements

Andre Deutschmann1, Michael Hans1, et al.

Bisphenol A (BPA), a high volume production chemical compound attracts growing attention as health relevant xenobiotic in humans. It can directly bind to hormone receptors, enzymes and ion channels to become biologically active. In this study we show that BPA acts as a potent blocker of voltage-activated Ca2+channels. We determined the mechanisms of block and the structural elements of BPA essential for its action. Macroscopic Ba2+/ Ca2+currents through native L-, N-, P/Q-, T-type Ca2+channels in rat endocrine GH3 cells, mouse DRG neurons or cardiac myocytes and recombinant human R-type Ca2+channels expressed in HEK293 cells were rapidly and reversibly inhibited by BPA with similar potency (EC50 values: 26 to 35 μM). Pharmacological and biophysical analysis of R-type Ca2+ channels revealed that BPA interacts with the extracellular part of the channel protein. Its action does not require intracellular signaling pathways, is neither voltage- nor use-dependent and does not affect channel gating. This indicates that BPA interacts with the channel in its resting state by directly binding to an external site outside the pore forming region. Structure-effect analyses of various phenolic and bisphenolic compounds revealed that (i) a double-alkylated (R-C(CH3)2-R, R-C(CH3)(CH2CH3)-R), or double-trifluoromethylated sp3 hybridized carbon atom between the two aromatic rings and (ii) the two aromatic moieties in angulated orientation are optimal for BPA's effectiveness. Since BPA highly pollutes the environment and is incorporated into the human organism our data may provide a basis for future studies relevant for human health and development.

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    2013-07-02 yb6560
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    2014-04-08 jj000001
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    2013-05-08 zhaojie88
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近期,上海交通大学医学院附属瑞金医院内分泌代谢科宁光教授等开展的一项研究表明,长期接触双酚A 可致低水平白蛋白尿(尿白蛋白肌酐比值为9.71~29.9 mg/g)风险增加。相关论文发表在Kidney International杂志上。 双酚A 是一种广泛用于塑料制品行业的工业化学物质,常被用来生产聚碳酸酯塑料和环氧树脂,水瓶和很多食品容器中均含有双酚A。 该研究纳入上海3455 例年龄≥ 40