ArticlePloS one2014
Sodium-glucose transporter-2 (SGLT2; SLC5A2) enhances cellular uptake of aminoglycosides.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Promotion of Cx26 mutants located in TM4 region for membrane translocation successfully rescued hearing loss.Theranostics · 2025Article
- Adaptation responses to salt stress in the gut ofAnimal cells and systems · 2025Article
- Local Delivery of Therapeutics to the Cochlea Using Nanoparticles and Other Biomaterials.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea.The Laryngoscope · 2021Article
- Impact of an SGLT2-loss of function mutation on renal architecture, histology, and glucose homeostasis.Cell and tissue research · 2021Article
- Canagliflozin reduces cisplatin uptake and activates Akt to protect against cisplatin-induced nephrotoxicity.American journal of physiology. Renal physiology · 2020Article
- Toll-like Receptor 4 Signaling and Downstream Neutrophilic Inflammation Mediate Endotoxemia-Enhanced Blood-Labyrinth Barrier Trafficking.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2020Article
- Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss.Science advances · 2019Article
- Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells.The Journal of clinical investigation · 2017Article
- Aminoglycoside-Induced Cochleotoxicity: A Review.Frontiers in cellular neuroscience · 2017Review
- [Role of Autophagy in the Radiosensitivity of Human Lung Adenocarcinoma A549 Cells].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [Diagnostic Value of Folate Receptor-positive Circulating Tumor Cell in Lung Cancer: A Pilot Study].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [Methylation Status of the SOCS3 Gene Promoter in H2228 Cells and EML4-ALK-positive Lung Cancer Tissues].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [Clinical Assessment of Chemosensitivity Test in Xeno-free Culture of Autologous Malignant Effusion Cells from Patients with Advanced Lung Adenocarcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [Investigation of Gene Expression Profile of A549 Cells after Overexpression of GPC5 by High Throughput Transcriptome Sequencing].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [Radiosensitization Induced by ANTP-SmacN7 Fusion Peptide in H460 Cell Line].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [Comprehensive Identification of MicroRNAs Regulated by Long Non-coding RNA MALAT1].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [LRRC3B is Downregulated in Non-small Cell Lung Cancer and Connected with Cell Proliferation and Invasion].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [M3 Muscarnic Receptor Antagonist Mediates Cell Proliferation Apoptosis and Adhesion in Small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- [Effect of TRAF6 Downregulation on Malignant Biological Behavior of Lung Cancer Cell Lines].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2015Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Aminoglycoside antibiotics, like gentamicin, continue to be clinically essential worldwide to treat life-threatening bacterial infections. Yet, the ototoxic and nephrotoxic side-effects of these drugs remain serious complications. A major site of gentamicin uptake and toxicity resides within kidney proximal tubules that also heavily express electrogenic sodium-glucose transporter-2 (SGLT2; SLC5A2) in vivo. We hypothesized that SGLT2 traffics gentamicin, and promotes cellular toxicity. We confirmed in vitro expression of SGLT2 in proximal tubule-derived KPT2 cells, and absence in distal tubule-derived KDT3 cells. D-glucose competitively decreased the uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescent analog of glucose, and fluorescently-tagged gentamicin (GTTR) by KPT2 cells. Phlorizin, an SGLT2 antagonist, strongly inhibited uptake of 2-NBDG and GTTR by KPT2 cells in a dose- and time-dependent manner. GTTR uptake was elevated in KDT3 cells transfected with SGLT2 (compared to controls); and this enhanced uptake was attenuated by phlorizin. Knock-down of SGLT2 expression by siRNA reduced gentamicin-induced cytotoxicity. In vivo, SGLT2 was robustly expressed in kidney proximal tubule cells of heterozygous, but not null, mice. Phlorizin decreased GTTR uptake by kidney proximal tubule cells in Sglt2+/- mice, but not in Sglt2-/- mice. However, serum GTTR levels were elevated in Sglt2-/- mice compared to Sglt2+/- mice, and in phlorizin-treated Sglt2+/- mice compared to vehicle-treated Sglt2+/- mice. Loss of SGLT2 function by antagonism or by gene deletion did not affect gentamicin cochlear loading or auditory function. Phlorizin did not protect wild-type mice from kanamycin-induced ototoxicity. We conclude that SGLT2 can traffic gentamicin and contribute to gentamicin-induced cytotoxicity.
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