| Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis |
| Yan, PJ; Li, NN; Ma, M; Liu, ZL; Yang, HC; Li, JN; Wan, CL; Gao, SL; Li, S; Zheng, LT; Waddington, JL; Xu, L ; Zhen, XC
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| 2023
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| 发表期刊 | SIGNAL TRANSDUCTION AND TARGETED THERAPY
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| ISSN | 2095-9907
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| 卷号 | 8期号:1 |
| 摘要 | Substance use disorder remains a major challenge, with an enduring need to identify and evaluate new, translational targets for effective treatment. Here, we report the upregulation of Hypoxia-inducible factor-1 & alpha; (HIF-1 & alpha;) expression by roxadustat (Rox), a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1 & alpha;, administered either systemically or locally into selected brain regions, suppressed morphine (Mor)-induced conditioned place preference (CPP). A similar effect was observed with methamphetamine (METH). Moreover, Rox also inhibited the expression of both established and reinstated Mor-CPP and promoted the extinction of Mor-CPP. Additionally, the elevation of HIF-1 & alpha; enhanced hepcidin/ferroportin 1 (FPN1)-mediated iron efflux and resulted in cellular iron deficiency, which led to the functional accumulation of the dopamine transporter (DAT) in plasma membranes due to iron deficiency-impaired ubiquitin degradation. Notably, iron-deficient mice generated via a low iron diet mimicked the effect of Rox on the prevention of Mor- or METH-CPP formation, without affecting other types of memory. These data reveal a novel mechanism for HIF-1 & alpha; and iron involvement in substance use disorder, which may represent a potential novel therapeutic strategy for the treatment of drug abuse. The findings also repurpose Rox by suggesting a potential new indication for the treatment of substance use disorder. |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/14055
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| 专题 | 科研部门_学习记忆的分子神经机制（徐林）
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推荐引用方式
GB/T 7714 |
Yan, PJ,Li, NN,Ma, M,et al. Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(1).
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| APA |
Yan, PJ.,Li, NN.,Ma, M.,Liu, ZL.,Yang, HC.,...&Zhen, XC.(2023).Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis.SIGNAL TRANSDUCTION AND TARGETED THERAPY,8(1).
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| MLA |
Yan, PJ,et al."Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis".SIGNAL TRANSDUCTION AND TARGETED THERAPY 8.1(2023).
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