The ABC transporter Abcg2/Bcrp: Role in hypoxia mediated survival
The ABC transporter Abcg2/Bcrp: Role in hypoxia mediated survival
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DOI：
10.1007/s10534-005-3709-7
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发表时间：
2005-08-01
期刊：
影响因子：
3.5
通讯作者：
Schuetz, JD
中科院分区：
文献类型：
--
作者：
Krishnamurthy, P;Schuetz, JD
ABC（ATP结合盒）转运蛋白在许多细胞过程中具有不同的作用。这些不同的作用需要保守的跨膜结构域和核苷酸结合结构域的存在。Bcrp（Abcg 2）是质膜转运蛋白的ATP结合盒家族的成员，其最初因其在肿瘤细胞中赋予耐药性的能力而被发现。随后的研究显示Bcrp在正常组织中表达，在原始干细胞中高表达。在低氧条件下诱导Bcrp表达，这与其在暴露于低氧环境的组织中的高表达一致。此外，Bcrp与血红素和其他卟啉相互作用。这一发现及其通过缺氧的调节表明，它可能在保护细胞/组织免受缺氧条件下原卟啉积累方面发挥作用。卟啉在Bcrp敲除小鼠的组织中积累的事实加强了这些观察。Bcrp等位基因功能缺失的人可能对卟啉诱导的光毒性更敏感。我们认为Bcrp在卟啉体内平衡中起作用，并调节低氧条件下的生存。
ABC (ATP-binding cassette) transporters have diverse roles in many cellular processes. These diverse roles require the presence of conserved membrane spanning domains and nucleotide binding domains. Bcrp (Abcg2) is a member of the ATP binding cassette family of plasma membrane transporters that was originally discovered for its ability to confer drug resistance in tumor cells. Subsequent studies showed Bcrp expression in normal tissues and high expression in primitive stem cells. Bcrp expression is induced under low oxygen conditions consistent with its high expression in tissues exposed to low oxygen environments. Moreover, Bcrp interacts with heme and other porphyrins. This finding and its regulation by hypoxia suggests it may play a role in protecting cells/tissue from protoporphyrin accumulation under hypoxia. These observations are strengthened by the fact that porphyrins accumulate in tissues of the Bcrp knockout mouse. It is possible that humans with loss of function Bcrp alleles may be more susceptible to porphyrin-induced phototoxicity. We propose that Bcrp plays a role in porphyrin homoeostasis and regulates survival under low oxygen conditions.