ABCB4, also called multidrug-resistant protein 3 (MDR3), is an ATP binding cassette transporter located in the canalicular membrane of hepatocytes that specifically translocates phosphatidylcholine (PC) lipids from the cytoplasmic to the extracellular leaflet. Due to the harsh detergent effect of bile acids, PC lipids provided by ABCB4 are extracted into the bile. While it is well known that bile acids are the major extractor of PC lipids from the membrane into bile, it is unknown whether only PC lipid extraction is improved or whether bile acids also have a direct effect on ABCB4. Using in vitro experiments, we investigated the modulation of ATP hydrolysis of ABC by different bile acids commonly present in humans. We demonstrated that all tested bile acids stimulated ATPase activity except for taurolithocholic acid, which inhibited ATPase activity due to its hydrophobic nature. Additionally, we observed a nearly linear correlation between the critical micelle concentration and maximal stimulation by each bile acid, and that this modulation was maintained in the presence of PC lipids. This study revealed a large effect of 24-nor-ursodeoxycholic acid, suggesting a distinct mode of regulation of ATPase activity compared with other bile acids. In addition, it sheds light on the molecular cross talk of canalicular ABC transporters of the human liver.

中文翻译：

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单体胆汁酸调节去污剂溶解的 ABCB4/MDR3 的 ATP 酶活性。

ABCB4，也称为耐多药蛋白 3 (MDR3)，是一种 ATP 结合盒转运蛋白，位于肝细胞的小管膜中，可特异性地将磷脂酰胆碱 (PC) 脂质从细胞质转运至细胞外小叶。由于胆汁酸的强烈去污作用，ABCB4 提供的 PC 脂质被提取到胆汁中。虽然众所周知胆汁酸是将 PC 脂质从膜中提取到胆汁中的主要提取物，但尚不清楚是否只有 PC 脂质提取得到改善，或者胆汁酸是否也对 ABCB4 有直接影响。通过体外实验，我们研究了人类常见的不同胆汁酸对 ABC 的 ATP 水解的调节作用。我们证明，除了牛磺石胆酸外，所有测试的胆汁酸都刺激了 ATP 酶活性，由于其疏水性，它抑制了 ATPase 的活性。此外，我们观察到临界胶束浓度与每种胆汁酸的最大刺激之间几乎呈线性相关，并且这种调节在 PC 脂质存在的情况下得以维持。这项研究揭示了 24-nor-熊去氧胆酸的巨大作用，表明与其他胆汁酸相比，ATP 酶活性的调节模式不同。此外，它还揭示了人类肝脏小管 ABC 转运蛋白的分子串扰。表明与其他胆汁酸相比，ATP酶活性的调节模式不同。此外，它还揭示了人类肝脏小管 ABC 转运蛋白的分子串扰。表明与其他胆汁酸相比，ATP酶活性的调节模式不同。此外，它还揭示了人类肝脏小管 ABC 转运蛋白的分子串扰。