Uptake transporters

Insulin-like growth factor 1 (IGF-1) is a critical fetal anabolic hormone. IGF-1 infusion to the normally growing sheep fetus increases the weight of some organs but does not consistently increase body weight. However, IGF-1 infusion profoundly decreases fetal plasma insulin concentrations, which may limit fetal growth potential. In this study, normally growing late gestation fetal sheep received an intravenous infusion of either: IGF-1 (IGF), IGF-1 with insulin and dextrose to maintain fetal euinsulinemia and euglycemia (IGF+INS), or vehicle control (CON) for one week...

The antipsychotic drug clozapine demonstrates superior efficacy in treatment-resistant schizophrenia, but its intracellular mode of action is not completely understood. Here, we analysed the effects of clozapine (2.5-20 µM) on metabolic fluxes, cell respiration, and intracellular ATP in human HL60 cells. Some results were confirmed in leukocytes of clozapine-treated patients. Neuroreceptor inhibition under clozapine reduced Akt activation with decreased glucose uptake, thereby inducing ER stress and the unfolded protein response (UPR)...

Cellular and organismic copper (Cu) homeostasis is regulated by Cu transporters and Cu chaperones to ensure the controlled uptake, distribution and export of Cu ions. Many of these processes have been extensively investigated in mammalian cell culture, as well as in humans and in mammalian model organisms. Most of the human genes encoding proteins involved in Cu homeostasis have orthologs in the model organism, Caenorhabditis elegans ( C. elegans ). Starting with a compilation of human Cu proteins and their orthologs, this review presents an overview of Cu homeostasis in C...

The hmuR operon encodes proteins for the uptake and utilization of heme as a nutritional iron source in Bradyrhizobium japonicum. The hmuR operon is transcriptionally activated by the Irr protein and is also positively controlled by HmuP by an unknown mechanism. An hmuP mutant does not express the hmuR operon genes nor does it grow on heme. Here, we show that hmuR expression from a heterologous promoter still requires hmuP, suggesting that HmuP does not regulate at the transcriptional level. Replacement of the 5' untranslated region (5'UTR) of an HmuP-independent gene with the hmuR 5'UTR conferred HmuP-dependent expression on that gene...

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1 H )-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo...

BACKGROUND: Dry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients' quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier...

The Ser/Thr kinase protein kinase-D1 (PKD1) is involved in induction of various cell physiological processes in the heart such as myocellular hypertrophy and inflammation, which may turn maladaptive during long-term stimulation. Of special interest is a key role of PKD1 in the regulation of cardiac substrate metabolism. Glucose and fatty acids are the most important substrates for cardiac energy provision, and the ratio at which they are utilized determines the health status of the heart. Cardiac glucose uptake is mainly regulated by translocation of the glucose transporter GLUT4 from intracellular stores (endosomes) to the sarcolemma, and fatty acid uptake via a parallel translocation of fatty acid transporter CD36 from endosomes to the sarcolemma...

BACKGROUND: The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([68 Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor. RESULTS: The radiochemical yield of [68 Ga]Ga-NOTA-Spermine was determined to be 64-69 %, demonstrating exceptional stability and radiochemical purity (>98 %)...

A yellow pigmented, Gram-stain-positive, motile, facultatively anaerobic and irregular rod-shaped bacteria (strain M0-14T ) was isolated from a till sample collected from the foreland of a high Arctic glacier near the settlement of Ny-Ålesund in the Svalbard Archipelago, Norway. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that M0-14T formed a lineage within the family Cellulomonadaceae , suborder Micrococcineae . M0-14T represented a novel member of the genus Pengzhenrongella and had highest 16S rRNA gene sequence similarity to Pengzhenrongella sicca LRZ-2T (97...

INTRODUCTION: Despite the well-recognized health benefits, the mechanisms and site of action of metformin remains elusive. Metformin-induced global lipidomic changes in plasma of animal models and human subjects have been reported. However, there is a lack of systemic evaluation of metformin-induced lipidomic changes in different tissues. Metformin uptake requires active transporters such as organic cation transporters (OCTs), and hence, it is anticipated that metformin actions are tissue-dependent...

Invasive pituitary neuroendocrine tumors (PitNETs) are the most prevalent types of intracranial and neuroendocrine tumors. Due to its aggressive growth and difficulty in complete resection, resulting in a high recurrence rate. The cystine transporter solute carrier family 7 member 11 (SLC7A11) is overexpression in various cancers, which contributes tumor growth, progression, and metastasis by promoting cystine uptake and glutathione biosynthesis. We identified SLC7A11 as an invasive biomarker based on three GEO cohorts...

Vitamin B12 (B12 ) serves as a critical cofactor within mycobacterial metabolism. While some pathogenic strains can synthesize B12 de novo , others rely on host-acquired B12 . In this investigation, we studied the transport of vitamin B12 in Mycobacterium marinum using B12 -auxotrophic and B12 -sensitive strains by deleting metH or metE , respectively. These two enzymes rely on B12 in different ways to function as methionine synthases. We used these strains to select mutants affecting B12 scavenging and confirmed their phenotypes during growth experiments in vitro ...

Aim: To establish a methodology for understanding how ultrasound (US) induces drug release from nano-sized drug-delivery systems (NSDDSs) and enhances drug penetration and uptake in tumors. This aims to advance cancer treatment strategies. Materials & methods: We developed a multi-physics mathematical model to elucidate and understand the intricate mechanisms governing drug release, transport and delivery. Unique in vitro models (monolayer, multilayer, spheroid) and a tailored US exposure setup were introduced to evaluate drug penetration and uptake...

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament...

Small extracellular vesicles (sEVs) are an important part of intercellular communication. They are phospholipid bilayer particles that carry active biomolecules such as proteins, various nucleic acids, and lipids. In recipient cells, sEVs can alter cellular functions, including cancer development and premetastatic niche formation in distant organs. Moreover, sEVs can carry cancer-specific features, which makes them promising biomarker candidates. However, the interactions of sEVs with biological barriers and consequences thereof, are not clarified yet...

Introduction: Solute carrier (SLC) transport proteins play a crucial role in maintaining cellular nutrient and metabolite homeostasis and are implicated in various human diseases, making them potential targets for therapeutic interventions. However, the study of SLCs has been limited due to the lack of suitable tools, particularly cell-based substrate uptake assays, necessary for understanding their biological functions and for drug discovery purposes. Methods: In this study, a cell-based uptake assay was developed using a stable isotope-labeled compound as the substrate for SLCs, with detection facilitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms...

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+ . Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+ , as supported by X-ray crystallography and ICP-MS...

This experiment prepared magnetic composite siderophores (DMPs) with strong magnetism, excellent adsorption capacity, and high specific surface area. Exploring the synergistic effect of magnetic nanoparticles and siderophores on Microcystis aeruginosa growth under iron-deficient condition, by utilizing the characteristics of the three-layer core-shell structure of DMPs. This study elucidated the potential mechanism by which DMPs promote the cyanobacterial growth through physiological indicators and transcriptome analysis...

Iron is an essential element for proper cell functioning, but unbalanced levels can cause cell death. Iron metabolism is controlled at the blood-tissue barriers provided by microvascular endothelial cells. Dysregulated iron metabolism at these barriers is a factor in both neurodegenerative and cardiovascular diseases. Mammalian iron efflux is mediated by the iron efflux transporter ferroportin (Fpn). Inflammation is a factor in many diseases and correlates with increased tissue iron accumulation. Evidence suggests treatment with IL-6 increases intracellular calcium levels and calcium is known to play an important role in protein trafficking...