[内源性代谢物转运体分析用于开发新的药物治疗和药物靶点]。

IF 0.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Kei Higuchi
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引用次数: 0

摘要

转运蛋白对于维持细胞、细胞器和细胞外液内代谢物的稳态至关重要。多种转运蛋白已被开发为药物治疗的靶标,包括葡萄糖转运蛋白(SLC5A2/SGLT2)和尿酸转运蛋白(SLC22A12/URAT1)。溶质载体转运蛋白家族包括许多具有未知生理功能和底物的孤儿转运蛋白,这主要是因为难以优化转运蛋白探针和构建方便的功能分析评估系统。然而,对这些转运蛋白的分析很重要,因为它们可能是药物治疗或药物靶点的潜在候选者。这篇综述的重点是对SLC16A家族的分析,该家族编码单羧酸转运蛋白(mct),因为它包含已知与几种疾病病理相关的孤儿转运蛋白。我们成功地鉴定出牛磺酸、头孢定和5-羧基荧光素分别是大鼠Slc16a6/MCT7、SLC16A13/MCT13和SLC16A5/MCT6的新底物。这些底物使哺乳动物细胞中转运蛋白的功能分析成为可能。我们发现辅助蛋白的共表达,如辅助蛋白basigin/CD147和embigin/GP70,增强了这些转运蛋白的转运功能。有趣的是,MCT6和MCT13的功能分别受到细胞外氯离子和钾离子的影响,但MCT7不受影响。这些发现有助于阐明孤儿和未表征mct的病理生理作用和底物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Analysis of Endogenous Metabolite Transporters for the Development of Novel Pharmaceutical Therapies and Drug Targets].

Transporters are critical for maintaining the homeostasis of metabolites within cells, organelles, and extracellular fluids. Various transporters have been targeted for development as pharmaceutical therapies, including glucose transporter (SLC5A2/SGLT2) and urate transporter (SLC22A12/URAT1). The solute carrier transporter family includes many orphan transporters with unknown physiological functions and substrates, largely because of the difficulties in optimizing the transporter probes and constructing convenient evaluation systems for functional analysis. However, the analysis of these transporters is important as they may be potential candidates for pharmaceutical therapies or drug targets. This review focuses on the analysis of the SLC16A family, which encodes monocarboxylate transporters (MCTs), as it contains orphan transporters known to be associated with several disease pathologies. We successfully identified taurine, cephradine, and 5-carboxyfluorescein as new substrates for rat Slc16a6/MCT7, SLC16A13/MCT13, and SLC16A5/MCT6, respectively. These substrates enabled the functional analysis of the transporters in mammalian cells. We found that the co-expression of ancillary proteins, such as ancillary protein basigin/CD147 and embigin/GP70, enhanced the transport functions of these transporters. Interestingly, the functions of MCT6 and MCT13 were affected by extracellular chloride and potassium ions, respectively, but MCT7 was unaffected. These findings are helpful for elucidating the pathophysiological roles and substrates of orphan and uncharacterized MCTs.

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来源期刊
CiteScore
0.60
自引率
0.00%
发文量
169
审稿时长
1 months
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