Roles of the ABCG2 Transporter in Protoporphyrin IX Distribution and Toxicity.

IF 4.4 3区医学 Q1 PHARMACOLOGY & PHARMACY Drug Metabolism and Disposition Pub Date : 2024-10-16 DOI:10.1124/dmd.123.001582

Qian Qi, Ruizhi Gu, Junjie Zhu, Karl E Anderson, Xiaochao Ma

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Abstract

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.

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ABCG2 转运体在原卟啉 IX 分布和毒性中的作用。

ATP 结合盒转运体 G 亚家族成员 2（ABCG2）是一种膜结合转运体，负责各种异种生物和内生生物的外流，包括血红素生物合成途径中的中间体原卟啉 IX（PPIX）。某些基因突变和化学物质会影响 PPIX 向血红素的转化和/或增加 PPIX 的产生，从而导致 PPIX 的积累和毒性。在小鼠体内，ABCG2 的缺乏可通过调节 PPIX 的分布，防止 PPIX 介导的光毒性和肝毒性。此外，体外研究表明，抑制 ABCG2 可将 PPIX 保留在靶细胞内，从而提高基于 PPIX 的光动力疗法的疗效。在这篇综述中，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。意义声明本综述总结了 ABCG2 在调节 PPIX 分布中的作用，并强调了 ABCG2 抑制剂在治疗 PPIX 介导的毒性方面的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Metabolism and Disposition 医学-药学

CiteScore

6.50

自引率

12.80%

发文量

128

审稿时长

3 months

期刊介绍： An important reference for all pharmacology and toxicology departments, DMD is also a valuable resource for medicinal chemists involved in drug design and biochemists with an interest in drug metabolism, expression of drug metabolizing enzymes, and regulation of drug metabolizing enzyme gene expression. Articles provide experimental results from in vitro and in vivo systems that bring you significant and original information on metabolism and disposition of endogenous and exogenous compounds, including pharmacologic agents and environmental chemicals.