更新于：2024-11-01

SLC22A5

更新于：2024-11-01

基本信息

别名

CDSP、High-affinity sodium-dependent carnitine cotransporter、OCTN2

+ [5]

简介

Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Retained in the ER, unable to perform carnitine uptake.

关联

项与 SLC22A5 相关的药物

Meldonium hydrate

米屈肼

靶点

BBOX x SLC22A5

作用机制

BBOX拮抗剂 [+1]

在研机构

Nanjing HUAXIN Biopharm. Co., Ltd. [+2]

原研机构-

在研适应症

酗酒 [+4]

非在研适应症

脑血管疾病

最高研发阶段批准上市

首次获批国家/地区-

首次获批日期1800-01-20

项与 SLC22A5 相关的临床试验

CTIS2023-509804-14-00 / Not yet recruitingIIT

The role of meldonium and individualized physical activities in the treatment of patients with heart failure - MELD-PHYS-2023

开始日期2024-03-27

申办/合作机构-

NCT06648902 / Completed临床1/2期IIT

A Phase 1/2 Study of the Safety and Preliminary Efficacy of Meldonium in Patients with Metastatic Renal Cell Carcinoma and Treatment-associated Fatigue.

Fatigue is a prevalent adverse event associated with systemic therapy using tyrosine kinase inhibitors (TKIs). Meldonium, a fatty acid oxidation inhibitor, modifies the carnitine pathway, a nutrient critical for fat metabolism. The World Anti-Doping Agency (WADA) classified meldonium as a banned substance due to its documented use by athletes aiming to enhance physical performance. In this study, the safety and preliminary efficacy of meldonium in treatment-related fatigue will be assessed.

开始日期2022-02-01

申办/合作机构-

CTR20140220 / Suspended临床3期

评估标准加米屈肼治疗慢性缺血性心力衰竭患者有效性和安全性的双盲、随机、安慰剂平行对照、多中心临床研究

主要目标：评估标准治疗加米屈肼相比较于标准治疗加安慰剂治疗慢性缺血性心衰病人 (NYHA II- III 级）的疗效次要目标：评估米屈肼治疗慢性缺血性心衰病人的安全性

开始日期2014-07-14

申办/合作机构

Jsc Grindeks

[+1]

100 项与 SLC22A5 相关的临床结果

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100 项与 SLC22A5 相关的转化医学

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0 项与 SLC22A5 相关的专利（医药）

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680

项与 SLC22A5 相关的文献（医药）

2024-12-01·Biochemical Pharmacology

Carnitine traffic and human fertility

Review

作者: Mazza, Tiziano ; Galluccio, Michele ; Indiveri, Cesare ; Tonazzi, Annamaria ; Pochini, Lorena ; Scalise, Mariafrancesca ; Console, Lara ; Giangregorio, Nicola

Carnitine is a vital molecule in human metabolism, prominently involved in fatty acid β-oxidation within mitochondria. Predominantly sourced from dietary intake, carnitine also derives from endogenous synthesis. This review delves into the complex network of carnitine transport and distribution, emphasizing its pivotal role in human fertility. Together with its role in fatty acid oxidation, carnitine modulates the acety-CoA/CoA ratio, influencing carbohydrate metabolism, lipid biosynthesis, and gene expression. The intricate regulation of carnitine homeostasis involves a network of membrane transporters, notably OCTN2, which is central in its absorption, reabsorption, and distribution. OCTN2 dysfunction, results in Primary Carnitine Deficiency (PCD), characterized by systemic carnitine depletion and severe clinical manifestations, including fertility issues. In the male reproductive system, carnitine is crucial for sperm maturation and motility. In the female reproductive system, carnitine supports mitochondrial function necessary for oocyte quality, folliculogenesis, and embryonic development. Indeed, deficiencies in carnitine or its transporters have been linked to asthenozoospermia, reduced sperm quality, and suboptimal fertility outcomes in couples. Moreover, the antioxidant properties of carnitine protect spermatozoa from oxidative stress and help in managing conditions like polycystic ovary syndrome (PCOS) and endometriosis, enhancing sperm viability and fertilization potential of oocytes. This review summarizes the key role of membrane transporters in guaranteeing carnitine homeostasis with a special focus on the implications in fertility and possible treatments of infertility and other related disorders.

2024-11-01·International Journal of Legal Medicine

Investigating cardiac genetic background in sudden infant death syndrome (SIDS)

Article

作者: Oliva, Antonio ; Nogué-Navarro, Laia ; Fernàndez-Falgueras, Anna ; Coll, Mònica ; Cazzato, Francesca ; Brugada, Ramon ; Castellà, Josep ; Grassi, Simone ; Iglesias, Anna

AbstractSudden infant death syndrome (SIDS) is still the leading cause of death for newborns in developed countries. The pathophysiological mechanisms have not been fully clarified, but in some of SIDS cases variants of genes associated with inherited cardiac conditions are found. In this study, an analysis of SCD-related genes was performed to determine the prevalence of rare pathogenic (P) or likely pathogenic (LP) variants that could provide an unambiguous explanation for the fatal event. A cohort of 76 SIDS cases underwent Next-Generation Sequencing (NGS) analysis with a custom panel of SCD-related genes. Rare variants were classified according to the guidelines provided by the American College of Medical Genetics and Genomics (ACMG) and the specifications of the ClinGen association. Post-mortem genetic testing identified 50 (65.8%) carriers of at least one variant in SCD genes. 104 rare genetic variants were found, 65.4% in genes encoding structural proteins. Only 4 out of 76 cases (5.3%) hosted at least a P or LP variant found in genes with structural or structural/arrhythmogenic functions (SLC22A5, SCN5A, MYL3and TTN). 99 variants were classified as of uncertain significance (VUS). The difference in the distribution of variants between gene groups by function was not statistically significant (chi square, p = 0,219). Despite this, most of the variants concerned structural genes that were supposed to have a close interaction with ion channels, thus providing an explanation for the arrhythmic event. Segregation analysis, reclassification of VUS variants and identification of new associated genes could clarify the implications of the current findings.

2024-10-16·Biological and Pharmaceutical Bulletin

Involvement of Proton-Coupled Organic Cation Antiporter in Human Blood–Brain Barrier Transport of Mesoridazine and Metoclopramide

Article

作者: Deguchi, Yoshiharu ; Amano, Nobuyuki ; Kubo, Yoshiyuki ; Igari, Tomoko ; Hirabayashi, Hideki ; Nakakariya, Masanori ; Aoyama, Kazunobu ; Kurosawa, Toshiki ; Debori, Yasuyuki

Mesoridazine and metoclopramide are cationic drugs that are distributed in the human brain despite being substrates of multidrug resistance protein 1 (MDR1), an efflux transporter expressed at the blood-brain barrier (BBB). We investigated their transport mechanisms at the BBB using hCMEC/D3, a human cerebral microvascular endothelial cell line often used as an in vitro BBB model. The cells exhibited time- and concentration-dependent uptake of mesoridazine and metoclopramide, with K_m values of 34 and 277 µM, respectively. The uptake of both drugs significantly decreased in the presence of typical inhibitors and/or substrates of the H⁺-coupled organic cation (H⁺/OC) antiporter but not in the presence of inhibitors or substrates of organic cation transporters (OCTs), OCTN2, OATPs, SLC35F2, or the plasma membrane monoamine transporter (PMAT). Furthermore, metoclopramide uptake by hCMEC/D3 cells was pH- and energy-dependent, whereas mesoridazine uptake was unaffected by intracellular acidification and treatment with metabolic inhibitors. These results suggest that the H⁺/OC antiporter is involved in the influx of mesoridazine and metoclopramide into the brain across the BBB.