Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Tapas Roy, Madhu Nath, Nabanita Halder, Rohit Saxena, Thirumurthy Velpandian
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Abstract

Peptide transporters are important plasma membrane proteins that facilitate the cellular uptake of di- and tripeptides in addition to various peptidomimetic drugs. The proton-coupled oligopeptide transporter (POT) family consists of mainly four transporter proteins, which include two H+ -coupled oligopeptide transporters known as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), along with two peptide/histidine transporters referred to as PHT1 (SLC15A4) and PHT2 (SLC15A3). These transporters play an important role in the drug delivery process in mammalian tissues. They are highly expressed in tissues such as the small intestine, kidney, liver, lung, and eye. PHT1 shows expression in immune cells, especially in B cells and plasmacytoid dendritic cells. The pathophysiological relevance of peptide transporters is emerging to be crucial in various disease conditions, e.g., PEPT1 plays a role in the physiopathology of the gastrointestinal system, particularly in IBD. Upregulated expression of peptide transporters has also been positively related to inflammatory responses. An increasing number of peptide-based drug therapies have been reported to have the potential for development of novel classes of drugs. For example, Carnosine (beta-alanyl-L-histidine) has been demonstrated to act as an antioxidant, antiglycating agent, and neuroprotector. It is transported by PEPT1 and PEPT2, facilitating its protective effects against oxidative stress in neurons and intestinal epithelial cells. Moreover, it has applications in the treatment of multidrug-resistant cancers and has been shown to improve glucose metabolism. This review gives an insight into the functional, physiological and pharmacological importance of proton-coupled oligopeptide transporter.

寡肽转运体的功能和生理意义:药物干预的潜在靶点。
肽转运蛋白是重要的质膜蛋白,促进细胞摄取二肽和三肽以及各种拟肽药物。质子偶联寡肽转运蛋白(POT)家族主要由四种转运蛋白组成,其中包括两个H+偶联寡肽转运蛋白PEPT1 (SLC15A1)和PEPT2 (SLC15A2),以及两个肽/组氨酸转运蛋白PHT1 (SLC15A4)和PHT2 (SLC15A3)。这些转运蛋白在哺乳动物组织的药物传递过程中起着重要作用。它们在小肠、肾脏、肝脏、肺和眼睛等组织中高度表达。PHT1在免疫细胞中表达,尤其是在B细胞和浆细胞样树突状细胞中。肽转运体的病理生理相关性在各种疾病条件下变得至关重要,例如,PEPT1在胃肠道系统的生理病理中发挥作用,特别是在IBD中。多肽转运蛋白的上调表达也与炎症反应呈正相关。据报道,越来越多的基于肽的药物疗法具有开发新型药物的潜力。例如,肌肽(β -丙酰- l-组氨酸)已被证明具有抗氧化剂、抗糖化剂和神经保护剂的作用。它通过PEPT1和PEPT2转运,促进其对神经元和肠上皮细胞氧化应激的保护作用。此外,它还应用于治疗耐多药癌症,并已被证明可以改善葡萄糖代谢。本文综述了质子偶联寡肽转运体的功能、生理和药理意义。
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
Journal of Membrane Biology
Journal of Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
4.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.
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