SLC5A3

更新于：2025-05-07

基本信息

别名

Na(+)/myo-inositol cotransporter、SLC5A3、SMIT

+ [6]

简介

Electrogenic Na(+)-coupled sugar symporter that actively transports myo-inositol and its stereoisomer scyllo-inositol across the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1 (By similarity). Maintains myo-inositol concentration gradient that defines cell volume and fluid balance during osmotic stress, in particular in the fetoplacental unit and central nervous system (By similarity). Forms coregulatory complexes with voltage-gated K(+) ion channels, allosterically altering ion selectivity, voltage dependence and gating kinetics of the channel. In turn, K(+) efflux through the channel forms a local electrical gradient that modulates electrogenic Na(+)-coupled myo-inositol influx through the transporter (PubMed:24595108, PubMed:28793216). Associates with KCNQ1-KCNE2 channel in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity) (PubMed:24595108). Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (PubMed:28793216). Provides myo-inositol precursor for biosynthesis of phosphoinositides such as PI(4,5)P2, thus indirectly affecting the activity of phosphoinositide-dependent ion channels and Ca(2+) signaling upon osmotic stress (PubMed:27217553).

关联

100 项与 SLC5A3 相关的临床结果

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100 项与 SLC5A3 相关的转化医学

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0 项与 SLC5A3 相关的专利（医药）

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214

项与 SLC5A3 相关的文献（医药）

2024-10-01·Fish & Shellfish Immunology

Myo-inositol: A potential game-changer in preventing gill cell death and alleviating “gill rot” in grass carp (Ctenopharyngodon idellus)

Article

Increasing evidence shows the potential threat of gill rot in freshwater fish culture. F. columnare is wide-spread in aquatic environments, which can cause fish gill rot and result in high mortality and losses of fish. This study investigated the effects of myo-inositol (MI) on the proliferation, structural integrity, and different death modes of grass carp (Ctenopharyngodon idella) gill epithelial cells, as well as its possible mechanism. 30 mg/L MI up-regulated CCK8 OD value and the protein level of solute carrier family 5A 3 (SLC5A3), and down-regulated the reactive oxygen species (ROS) content in gill cells and lactate dehydrogenase (LDH) release in the culture medium (P < 0.05). MI up-regulated the protein level of Beclin1, the protein level and fluorescence expression of microtubule-associated protein light chain 3B (LC3B) and down-regulated the protein level of sequestosome-1 (SQSTM1, also called p62) (P < 0.05). MI down-regulated the protein levels of Cysteine aspartate protease-1 (caspase-1), Gasdermin E (GSDME) and Cleaved interleukin 1 beta (IL-1β) (P < 0.05). MI up-regulated the protein level of caspase-8 (P < 0.05), but had no effect on apoptosis (P > 0.05). MI down-regulated the mRNA expressions and protein levels of tumor necrosis factor α (tnfα), TNF receptor 1 (tnfr1), receptor interacting protein 1 (ripk1), receptor interacting protein 3 (ripk3) and mixed lineage kinase domain-like protein (mlkl), and reduce the ratio of p-MLKL/MLKL (P < 0.05). The addition of MI or necrosulfonamide (NSA) alone, or the addition of MI after induction of necroptosis, significantly up-regulated the cell activity and the protein level of SLC5A3 in gill cells, and significantly reduced the LDH release in the culture medium and the intracellular ROS content, the number of necroptosis cells, the protein expression of TNFα, TNFR1 and RIPK1, and the ratio of p-RIPK3/RIPK3 and p-MLKL/MLKL (P < 0.05). It indicated MI induce autophagy may relate to Beclin1/LC3/p62 signaling pathway, inhibits pyroptosis may attribute to Caspase-1/GSDMD/IL-1β signaling pathway, and inhibits necroptosis via MLKL signaling pathway. However, MI had no effect on apoptosis.

2024-09-01·eBioMedicine

Plasma myo-inositol elevation in heart failure: clinical implications and prognostic significance. Results from the BElgian and CAnadian MEtabolomics in HFpEF (BECAME-HF) research project

Article

作者: Mahrouche, Louiza ; Roy, Clotilde ; Furtos, Alexandra ; Legault, Julie Thompson ; Boucher, Gabrielle ; Charpentier, Daniel ; Hussin, Julie ; Rosiers, Christine Des ; Pouleur, Anne-Catherine ; Gruson, Damien ; Tardif, Jean-Claude ; Marino, Alice ; Cumps, Julien ; Badii, Maria ; Beauloye, Christophe ; Battault, Sylvain ; Menghoum, Nassiba ; Horman, Sandrine ; Rhainds, David ; Pedneault-Gagnon, Valérie ; Bertrand, Luc ; Lejeune, Sibille

BACKGROUNDThe metabolic environment plays a crucial role in the development of heart failure (HF). Our prior research demonstrated that myo-inositol, a metabolite transported by the sodium-myo-inositol co-transporter 1 (SMIT-1), can induce oxidative stress and may be detrimental to heart function. However, plasmatic myo-inositol concentration has not been comprehensively assessed in large cohorts of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).METHODSPlasmatic myo-inositol levels were measured using mass spectrometry and correlated with clinical characteristics in no HF subjects and patients with HFrEF and HFpEF from Belgian (male, no HF, 53%; HFrEF, 84% and HFpEF, 40%) and Canadian cohorts (male, no HF, 51%; HFrEF, 92% and HFpEF, 62%).FINDINGSMyo-inositol levels were significantly elevated in patients with HF, with a more pronounced increase observed in the HFpEF population of both cohorts. After adjusting for age, sex, body mass index, hypertension, diabetes, and atrial fibrillation, we observed that both HFpEF status and impaired kidney function were associated with elevated plasma myo-inositol. Unlike HFrEF, abnormally high myo-inositol (≥69.8 μM) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence interval, [1.05-2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fibrosis in this subset of patients.INTERPRETATIONMyo-inositol is a metabolite elevated in patients with HF and strongly correlated to kidney failure. In patients with HFpEF, high myo-inositol levels predict poor clinical outcomes and are linked to markers of cardiac adverse remodelling. This suggests that myo-inositol and its transporter SMIT1 may have a role in the pathophysiology of HFpEF.FUNDINGBECAME-HF was supported by Collaborative Bilateral Research Program Québec - Wallonie-Brussels Federation.

2024-07-01·Chemical Biology & Drug Design

Integrative analysis of ex vivo studies and microarray reveals the novel inhibitor effects of trehalose on the pathogenesis of pterygium

Article

作者: Tokgun, Onur ; Yılmaz, Banu Candan ; İnci, Kubilay ; Yilmaz, Ugur ; Durkal, Yasin

AbstractPterygium is a frequent eye surface condition that is characterized by a high rate of proliferation, fibrovascular development, cellular migration, corneal infiltration, and angiogenesis. We investigated that ex vivo primary pterygium and conjunctival cell cultures were generated to analyze the effect of trehalose on cellular proliferation. After trehalose treatment, we performed microarray analysis to evaluate changes in the mRNA profile. We analyzed gene ontology (GO) and KEGG pathways to identify hub genes that changed expression levels after treatment and were associated with pterygium development. We selected three genes to verify their expression levels using qRT–PCR. The study also evaluated the impact of trehalose treatment on cell migration through a wound‐healing assay. Our results suggested that pterygium cell proliferation was inhibited in a dose‐dependent manner by trehalose. 2354 DEG were identified in pterygium and conjunctiva cells treated with trehalose compared to untreated groups. Functional enrichment analysis showed that differentially expressed mRNAs are involved in proliferation, vasculature development, and cell migration. We identified ten hub genes including upregulated (RANBP3L, SLC5A3, RERG, ANKRD1, DHCR7, RAB27B, GPRC5B, MSMO1, ASPN, DRAM1) and downregulated (TNC, PTGS2, GREM2, NPTX1, NR4A1, HMOX1, CXCL12, IL6, MYH2, TXNIP). Microarray analysis and functional investigations suggest that trehalose affects the pathogenesis of pterygium by modifying the expression of genes involved in crucial pathways related to cell function.

项与 SLC5A3 相关的新闻（医药）

2023-07-11

·生物谷

Int. J. Biol. Sci: SLC5A3对宫颈癌细胞的生长至关重要

据估计，在全球范围内，每年有超过32万人死于宫颈癌。妇女宫颈癌的发病率(13.1%)和死亡率(6.1%)在癌症中排名第四。目前，晚期、复发或转移性宫颈癌患者尚无根治性治疗策略。据估计，在全球范围内，每年有超过32万人死于宫颈癌。妇女宫颈癌的发病率(13.1%)和死亡率(6.1%)在癌症中排名第四。目前，晚期、复发或转移性宫颈癌患者尚无根治性治疗策略。目前的治疗方法，包括传统的顺铂/紫杉醇化疗、贝伐单抗靶向治疗和免疫治疗(免疫检查点抑制剂)，在这些患者中的有效率<50%。因此，有必要确定新的信号转导靶点，并开发相应的靶向治疗晚期、复发和转移性宫颈癌。图片来源：https://pubmed.ncbi.nlm.nih.gov/37324953/ 近日，来自复旦大学的研究者们在Int. J. Biol. Sci.杂志上发表了题为“SLC5A3 is important for cervical cancer cell growth”的文章，该研究揭示了过表达的SLC5A3促进了宫颈癌细胞的生长，成为这种毁灭性疾病的新的治疗肿瘤靶点。必须确定宫颈癌的新分子靶点。本研究探讨了肌醇转运蛋白SLC5A3在宫颈癌发病机制中的作用。通过生物信息学分析，研究者发现SLC5A3在宫颈癌组织中表达上调。SLC5A3基因表达上调与生存期和无进展间期呈负相关。与SLC5A3共表达的基因在参与癌症进展的多个信号级联中得到丰富。在原代/已建立的宫颈癌细胞中，SLC5A3 shRNA/KO具有生长抑制和促进细胞死亡/凋亡的作用。此外，SLC5A3基因敲除或KO下调宫颈癌细胞的肌醇水平，诱导氧化损伤，并降低Akt-mTOR的激活。相反，补充肌醇或N-乙酰-L-半胱氨酸或转导具有结构活性的Akt1结构可减轻SLC5A3KO对宫颈癌细胞的细胞毒作用。慢病毒SLC5A3过表达构建的转导系统上调细胞肌醇水平，促进Akt-mTOR激活，促进宫颈癌细胞的增殖和迁移。TONEBP与SLC5A3启动子的结合在宫颈癌中上调。体内研究表明，瘤内注射表达SLC5A3 shRNA的病毒可抑制小鼠宫颈癌移植瘤的生长。 SLC5A3KO还能抑制pCCA-1宫颈癌移植瘤的生长。缺失SLC5A3的异种移植组织表现为肌醇下调、Akt-mTOR失活和氧化损伤。转导Sh-TONEBP AAV可下调SLC5A3的表达并抑制pCCA-1宫颈癌移植瘤的生长。 SLC5A3在宫颈癌中表达上调图片来源：https://pubmed.ncbi.nlm.nih.gov/37324953/ 本研究证实TONEBP是宫颈癌中SLC5A3的关键转录因子。TONEBP是TCGA队列中与SLC5A3呈正相关的第二大DEG。在宫颈癌细胞中，TONEBP基因敲除后SLC5A3mRNA和蛋白表达水平下调，而异位TONEBP过表达则上调。 TONEBP与SLC5A3启动子的结合在多种宫颈癌组织/细胞中上调，可能与SLC5A3上调有关。在体内，TONEBP基因敲除可抑制SLC5A3的表达，抑制pCCA-1肿瘤的生长。因此，TONEBP上调SLC5A3的表达，促进宫颈癌细胞的生长。（生物谷 Bioon.com）参考文献 Li Li et al. SLC5A3 is important for cervical cancer cell growth. Int J Biol Sci. 2023 May 27;19(9):2787-2802. doi: 10.7150/ijbs.84570.