Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (Q.Q., R.G., J.Z., X.M.) and Porphyria Laboratory and Center, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas (K.E.A.).
Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (Q.Q., R.G., J.Z., X.M.) and Porphyria Laboratory and Center, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas (K.E.A.)
Drug Metab Dispos. 2024 Oct 16;52(11):1201-1207. doi: 10.1124/dmd.123.001582.
ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a membrane-bound transporter responsible for the efflux of various xenobiotics and endobiotics, including protoporphyrin IX (PPIX), an intermediate in the heme biosynthesis pathway. Certain genetic mutations and chemicals impair the conversion of PPIX to heme and/or increase PPIX production, leading to PPIX accumulation and toxicity. In mice, deficiency of ABCG2 protects against PPIX-mediated phototoxicity and hepatotoxicity by modulating PPIX distribution. In addition, in vitro studies revealed that ABCG2 inhibition increases the efficacy of PPIX-based photodynamic therapy by retaining PPIX inside target cells. In this review, we discuss the roles of ABCG2 in modulating the tissue distribution of PPIX, PPIX-mediated toxicity, and PPIX-based photodynamic therapy. SIGNIFICANCE STATEMENT: This review summarized the roles of ABCG2 in modulating PPIX distribution and highlighted the therapeutic potential of ABCG2 inhibitors for the management of PPIX-mediated toxicity.
三磷酸腺苷结合盒转运蛋白 G 超家族成员 2（ABCG2）是一种膜结合转运蛋白，负责将各种外源性和内源性物质排出细胞，包括原卟啉 IX（PPIX），它是血红素生物合成途径中的中间产物。某些基因突变和化学物质会损害 PPIX 转化为血红素和/或增加 PPIX 的产生，导致 PPIX 积累和毒性。在小鼠中，ABCG2 的缺乏通过调节 PPIX 的分布来保护细胞免受 PPIX 介导的光毒性和肝毒性。此外，体外研究表明，通过将 PPIX 保留在靶细胞内，ABCG2 抑制可提高基于 PPIX 的光动力疗法的疗效。在本综述中，我们讨论了 ABCG2 在调节 PPIX 的组织分布、PPIX 介导的毒性和基于 PPIX 的光动力疗法中的作用。
本综述总结了 ABCG2 在调节 PPIX 分布中的作用，并强调了 ABCG2 抑制剂在管理 PPIX 介导的毒性方面的治疗潜力。
