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1.
Biol Cell ; 116(6): e2470003, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653736

RESUMO

BACKGROUND INFORMATION: Aquaporins are H2O-permeable membrane protein pores. However, some aquaporins are also permeable to other substances such as CO2. In higher plants, overexpression of such aquaporins has already led to an enhanced photosynthetic performance due to improved CO2 mesophyll conductance. In this work, we investigated the effects of such aquaporins on unicellular photosynthetically active organisms, specifically cyanobacteria. RESULTS: Overexpression of aquaporins NtAQP1 or hAQP1 that might have a function to improve CO2 membrane permeability lead to increased photosynthesis rates in the cyanobacterium Synechococcus sp. PCC7002 as concluded by the rate of evolved O2. A shift in the Plastoquinone pool state of the cells supports our findings. Water permeable aquaporins without CO2 permeability, such as NtPIP2;1, do not have this effect. CONCLUSIONS AND SIGNIFICANCE: We conclude that also in single cell organisms like cyanobacteria, membrane CO2 conductivity could be rate limiting and CO2-porins reduce the respective membrane resistance. We could show that besides the tobacco aquaporin NtAQP1 also the human hAQP1 most likely functions as CO2 diffusion facilitator in the photosynthesis assay.


Assuntos
Aquaporinas , Nicotiana , Fotossíntese , Synechococcus , Synechococcus/metabolismo , Nicotiana/metabolismo , Humanos , Aquaporinas/metabolismo , Aquaporinas/genética , Dióxido de Carbono/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
2.
J Physiol ; 602(13): 3111-3129, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38323926

RESUMO

Aquaporin-3 (AQP3) is a membrane channel with dual aquaglyceroporin/peroxiporin activity, facilitating the diffusion of water, glycerol and H2O2 across cell membranes. AQP3 shows aberrant expression in melanoma and its role in cell adhesion, migration and proliferation is well described. Gold compounds were shown to modulate AQP3 activity with reduced associated toxicity, making them promising molecules for cancer therapy. In this study, we validated the phenotype resulting from AQP3-silencing of two melanoma cell lines, MNT-1 and A375, which resulted in decreased H2O2 permeability. Subsequently, the AQP3 inhibitory effect of a new series of organogold compounds derived from Auphen, a potent AQP3 inhibitor, was first evaluated in red blood cells (RBCs) that highly express AQP3, and then in HEK-293T cells with AQP3 overexpression to ascertain the compounds' specificity. The first screening in RBCs unveiled two organogold compounds as promising blockers of AQP3 permeability. Moderate reduction of glycerol permeability but drastic inhibition of H2O2 permeability was detected for some of the gold derivatives in both AQP3-overexpressing cells and human melanoma cell lines. Additionally, all compounds were effective in impairing cell adhesion, proliferation and migration, although in a cell type-dependent manner. In conclusion, our data show that AQP3 peroxiporin activity is crucial for melanoma progression and highlight organogold compounds as promising AQP3 inhibitors with implications in melanoma cell adhesion, proliferation and migration, unveiling their potential as anticancer drugs against AQP3-overexpressing tumours. KEY POINTS: AQP3 affects cellular redox balance. Gold compounds inhibit AQP3 permeability in melanoma cells. AQP3 is involved in cell adhesion, proliferation and migration of melanoma. Blockage of AQP3 peroxiporin activity impairs melanoma cell migration. Gold compounds are potential anticancer drug leads for AQP3-overexpressing cancers.


Assuntos
Aquaporina 3 , Adesão Celular , Movimento Celular , Proliferação de Células , Melanoma , Aquaporina 3/metabolismo , Aquaporina 3/genética , Humanos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células HEK293 , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia
3.
J Biol Chem ; 299(12): 105410, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913906

RESUMO

Aquaporins can facilitate the passive movement of water, small polar molecules, and some ions. Here, we examined solute selectivity for the barley Nodulin 26-like Intrinsic Protein (HvNIP2;1) embedded in liposomes and examined through stopped-flow light scattering spectrophotometry and Xenopus laevis oocyte swelling assays. We found that HvNIP2;1 permeates water, boric and germanic acids, sucrose, and lactose but not d-glucose or d-fructose. Other saccharides, such as neutral (d-mannose, d-galactose, d-xylose, d-mannoheptaose) and charged (N-acetyl d-glucosamine, d-glucosamine, d-glucuronic acid) aldoses, disaccharides (cellobiose, gentiobiose, trehalose), trisaccharide raffinose, and urea, glycerol, and acyclic polyols, were permeated to a much lower extent. We observed apparent permeation of hydrated KCl and MgSO4 ions, while CH3COONa and NaNO3 permeated at significantly lower rates. Our experiments with boric acid and sucrose revealed no apparent interaction between solutes when permeated together, and AgNO3 or H[AuCl4] blocked the permeation of all solutes. Docking of sucrose in HvNIP2;1 and spinach water-selective SoPIP2;1 aquaporins revealed the structural basis for sucrose permeation in HvNIP2;1 but not in SoPIP2;1, and defined key residues interacting with this permeant. In a biological context, sucrose transport could constitute a novel element of plant saccharide-transporting machinery. Phylogenomic analyses of 164 Viridiplantae and 2993 Archaean, bacterial, fungal, and Metazoan aquaporins rationalized solute poly-selectivity in NIP3 sub-clade entries and suggested that they diversified from other sub-clades to acquire a unique specificity of saccharide transporters. Solute specificity definition in NIP aquaporins could inspire developing plants for food production.


Assuntos
Aquaporinas , Hordeum , Metaloides , Água , Animais , Aquaporinas/metabolismo , Glucosamina , Hordeum/metabolismo , Metaloides/metabolismo , Sacarose , Água/metabolismo
4.
Chembiochem ; 25(10): e202400087, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38439618

RESUMO

The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in vivo. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction of cells express the reporter. To overcome this limitation, we developed an approach for amplifying the sensitivity of molecular MRI by combining a chemogenetic contrast mechanism with a biophysical approach to increase water diffusion through the co-expression of a dual-gene construct comprising an organic anion transporting polypeptide, Oatp1b3, and a water channel, Aqp1. We first show that the expression of Aqp1 amplifies MRI contrast in cultured cells engineered to express Oatp1b3. We demonstrate that the contrast amplification is caused by Aqp1-driven increase in water exchange, which provides the gadolinium ions internalized by Oatp1b3-expressing cells with access to a larger water pool compared with exchange-limited conditions. We further show that our methodology allows cells to be detected using approximately 10-fold lower concentrations of gadolinium than that in the Aqp1-free scenario. Finally, we show that our approach enables the imaging of mixed-cell cultures containing a low fraction of Oatp1b3-labeled cells that are undetectable on the basis of Oatp1b3 expression alone.


Assuntos
Aquaporina 1 , Genes Reporter , Imageamento por Ressonância Magnética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto , Água , Água/química , Humanos , Imageamento por Ressonância Magnética/métodos , Aquaporina 1/metabolismo , Aquaporina 1/genética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Gadolínio/química , Meios de Contraste/química , Meios de Contraste/metabolismo , Células HEK293 , Animais
5.
New Phytol ; 241(4): 1404-1414, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38155452

RESUMO

Light intensity and quality influence photosynthesis directly but also have an indirect effect by increasing stomatal apertures and enhancing gas exchange. Consequently, in areas such as the upper canopy, a high water demand for transpiration and temperature regulation is created. This paper explores how light intensity and the natural high Blue-Light (BL) : Red-Light (RL) ratio in these areas, is important for controlling leaf hydraulic conductance (Kleaf ) by BL signal transduction, increasing water permeability in cells surrounding the vascular tissue, in supporting the enormous water demands. Conversely, shaded inner-canopy areas receive less radiation, have lower water and cooling demands, and exhibit reduced Kleaf due to diminished intensity and BL induction. Intriguingly, shaded leaves display higher water-use efficiency (compared with upper-canopy) due to decreased transpiration and cooling requirements while the presence of RL supports photosynthesis.


Assuntos
Folhas de Planta , Água , Água/fisiologia , Folhas de Planta/fisiologia , Plantas , Transpiração Vegetal/fisiologia , Estômatos de Plantas/fisiologia
6.
Cell Commun Signal ; 22(1): 106, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336645

RESUMO

Aquaporins (AQPs) are ubiquitous channel proteins that play a critical role in the homeostasis of the cellular environment by allowing the transit of water, chemicals, and ions. They can be found in many different types of cells and organs, including the lungs, eyes, brain, glands, and blood vessels. By controlling the osmotic water flux in processes like cell growth, energy metabolism, migration, adhesion, and proliferation, AQPs are capable of exerting their regulatory influence over a wide range of cellular processes. Tumour cells of varying sources express AQPs significantly, especially in malignant tumours with a high propensity for metastasis. New insights into the roles of AQPs in cell migration and proliferation reinforce the notion that AQPs are crucial players in tumour biology. AQPs have recently been shown to be a powerful tool in the fight against pathogenic antibodies and metastatic cell migration, despite the fact that the molecular processes of aquaporins in pathology are not entirely established. In this review, we shall discuss the several ways in which AQPs are expressed in the body, the unique roles they play in tumorigenesis, and the novel therapeutic approaches that could be adopted to treat carcinoma.


Assuntos
Aquaporinas , Neoplasias , Humanos , Neoplasias/patologia , Carcinogênese , Transformação Celular Neoplásica , Água/metabolismo , Aquaporinas/química , Aquaporinas/metabolismo
7.
Dig Dis Sci ; 69(4): 1143-1155, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38421507

RESUMO

BACKGROUND: Intestinal mucosal barrier dysfunction plays a crucial role in the pathogenesis of irritable bowel syndrome with diarrhea (IBS-D). In order to explore the mechanism of electroacupuncture (EA) treatment on intestinal mucosal barrier, this study observed the effect of EA on aquaporins (AQPs), tight junctions (TJs), NF-κB pathway and the gut microbiota in IBS-D rats. METHODS: The IBS-D model was established by acetic acid enema combined with chronic restraint method. The effects of EA on the treatment of IBS-D were examined by the abdominal withdrawal reflex score, Bristol's fecal character score, fecal water content, small intestine propulsion rate and HE staining. AQPs, TJs and inflammation-related molecular mechanisms were explored. The fecal samples were applied for 16S rRNA sequencing to assess the effect of EA intervention to the intestinal bacterial abundance. RESULTS: EA reduced intestinal sensitization, restored intestinal motility and improved inflammatory cell infiltration. Furthermore, EA improved intestinal inflammation and flora environment significantly, inhibited NF-κB signaling and inflammatory factors (IL-1ß and TNF-α). It can also increase the gene and protein expression of AQPs (AQP1, AQP3, and AQP8) and the gene levels of TJs (ZO-1 and Occludin). CONCLUSION: EA has an inhibitory effect on the NF-κB signaling pathway, and regulates the proteins of AQP1, AQP3, AQP8, and TJs to restore the balance of water metabolism and intestinal permeability in IBS-D, which also restored the function of the intestinal mucosa by regulating the intestinal flora.


Assuntos
Aquaporinas , Eletroacupuntura , Síndrome do Intestino Irritável , Ratos , Animais , Síndrome do Intestino Irritável/metabolismo , NF-kappa B/metabolismo , Função da Barreira Intestinal , RNA Ribossômico 16S , Diarreia , Aquaporinas/metabolismo , Inflamação , Água
8.
Eur J Oral Sci ; 132(2): e12969, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38192116

RESUMO

The exocrine salivary gland secretes saliva, a fundamental body component to maintain oral homeostasis. Saliva is composed of water, ions, and proteins such as amylase, mucins, and immunoglobulins that play essential roles in the digestion of food, lubrication, and prevention of dental caries and periodontitis. An increasing number of people experience saliva hyposecretion due to aging, medications, Sjögren's syndrome, and radiation therapy for head and neck cancer. However, current treatments are mostly limited to temporary symptomatic relief. This review explores the molecular mechanisms underlying saliva secretion and hyposecretion to provide insight into putative therapeutic targets for treatment. Proteins implicated in saliva secretion pathways, including Ca2+ -signaling proteins, aquaporins, soluble N-ethylmaleimide-sensitive factor attachment protein receptors, and tight junctions, are aberrantly expressed and localized in patients with saliva hyposecretion, such as Sjögren's syndrome. Analysis of studies on the mechanisms of saliva secretion and hyposecretion suggests that crosstalk between fluid and protein secretory pathways via Ca2+ /protein kinase C and cAMP/protein kinase A regulates saliva secretion. Impaired crosstalk between the two secretory pathways may contribute to saliva hyposecretion. Future research into the detailed regulatory mechanisms of saliva secretion and hyposecretion may provide information to define novel targets and generate therapeutic strategies for saliva hyposecretion.


Assuntos
Cárie Dentária , Síndrome de Sjogren , Xerostomia , Humanos , Saliva/metabolismo , Glândulas Salivares/metabolismo
9.
Oral Dis ; 30(1): 50-62, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37518974

RESUMO

AIM: The aim of the study was to observe the effect of acupuncture on regulating interleukin (IL)-17, tumor necrosis factor (TNF)-ɑ, and aquaporins (AQPs) in Sjögren's syndrome (SS) on patients and on non-obese diabetic (NOD) models. METHODS: Levels of anti-AQP 1, 5, 8, and 9 antibodies, IL-17, and TNF-ɑ in the serum of SS patients were compared prior and following 20 acupuncture treatment visits during 8 weeks. While in murine model, five groups were divided to receive interventions for 4 weeks, including control, model, acupuncture, isoflurane, and hydroxychloroquine. The submaxillofacial gland index, histology, immunohistochemistry of AQP1, 5, salivary flow, together with IL-17, and TNF-ɑ expression in peripheral blood were compared among the groups. RESULTS: Acupuncture reduced IL-17, TNF-ɑ, and immunoglobin A levels, and numeric analog scale of dryness in 14 patients with SS (p < 0.05). The salivary flow was increased, and the water intake decreased in NOD mice receiving acupuncture treatments. IL-17 and TNF-ɑ levels in peripheral serum were down-regulated (p < 0.05) and AQP1, 5 expression in the submandibular glands up-regulated in mice. CONCLUSION: The effect on relieving xerostomia with acupuncture may be achieved by up-regulating the expression of AQP1. AQP5, down-regulating levels of IL-17 and TNF-ɑ, and a decrease in inflammation of glands.


Assuntos
Terapia por Acupuntura , Síndrome de Sjogren , Humanos , Animais , Camundongos , Síndrome de Sjogren/patologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-17/metabolismo , Camundongos Endogâmicos NOD , Glândula Submandibular/metabolismo , Modelos Animais de Doenças
10.
Int J Mol Sci ; 25(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38473914

RESUMO

The study of aquaporins (AQPs) in various forensic fields has offered a promising horizon in response to the need to have reliable elements for the identification of the manner of death and for the individuation of forensic markers for the timing of lesions and vitality of injury. In the literature, various tissues have been studied; the most investigated are the lungs, brain, kidneys, skin, and blood vessels. A systematic literature review on PubMed following PRISMA 2020 guidelines enabled the identification of 96 articles. In all, 34 of these were enrolled to identify Aquaporin-like (AQP-like) forensic markers. The analysis of the literature demonstrated that the most significant markers among the AQPs are as follows: for the brain, AQP4, which is very important in brain trauma and hypoxic damage; AQP3 in the skin lesions caused by various mechanisms; and AQP5 in the diagnosis of drowning. Other applications are in organ damage due to drug abuse and thrombus dating. The focus of this review is to collect all the data present in the literature about the forensic application of AQPs as forensic markers in the most important fields of application. In the current use, the individuation, validation, and application of markers in forensic investigation are very useful in real forensic applications in cases evaluated in court.


Assuntos
Aquaporinas , Humanos , Aquaporinas/metabolismo , Pulmão/patologia , Hipóxia/patologia , Encéfalo/metabolismo , Pele/metabolismo
11.
Int J Mol Sci ; 25(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38928364

RESUMO

Triple-negative breast cancer (TNBC) remains one of the most challenging subtypes since it is initially characterized by the absence of specific biomarkers and corresponding targeted therapies. Advances in methodology, translational informatics, genomics, and proteomics have significantly contributed to the identification of therapeutic targets. The development of innovative treatments, such as antibody-drug conjugates and immune checkpoint inhibitors, alongside chemotherapy, has now become the standard of care. However, the quest for biomarkers defining therapy outcomes is still ongoing. Peroxiporins, which comprise a subgroup of aquaporins, which are membrane pores facilitating the transport of water, glycerol, and hydrogen peroxide, have emerged as potential biomarkers for therapy response. Research on peroxiporins reveals their involvement beyond traditional channeling activities, which is also reflected in their cellular localization and roles in cellular signaling pathways. This research on peroxiporins provides fresh insights into the mechanisms of therapy resistance in tumors, offering potential avenues for predicting treatment outcomes and tailoring successful TNBC therapies.


Assuntos
Biomarcadores Tumorais , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/terapia , Biomarcadores Tumorais/metabolismo , Feminino , Aquaporinas/metabolismo , Transdução de Sinais , Animais
12.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731801

RESUMO

Leaf movement is a manifestation of plant response to the changing internal and external environment, aiming to optimize plant growth and development. Leaf movement is usually driven by a specialized motor organ, the pulvinus, and this movement is associated with different changes in volume and expansion on the two sides of the pulvinus. Blue light, auxin, GA, H+-ATPase, K+, Cl-, Ca2+, actin, and aquaporin collectively influence the changes in water flux in the tissue of the extensor and flexor of the pulvinus to establish a turgor pressure difference, thereby controlling leaf movement. However, how these factors regulate the multicellular motility of the pulvinus tissues in a species remains obscure. In addition, model plants such as Medicago truncatula, Mimosa pudica, and Samanea saman have been used to study pulvinus-driven leaf movement, showing a similarity in their pulvinus movement mechanisms. In this review, we summarize past research findings from the three model plants, and using Medicago truncatula as an example, suggest that genes regulating pulvinus movement are also involved in regulating plant growth and development. We also propose a model in which the variation of ion flux and water flux are critical steps to pulvinus movement and highlight questions for future research.


Assuntos
Medicago truncatula , Folhas de Planta , Pulvínulo , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/crescimento & desenvolvimento , Medicago truncatula/fisiologia , Medicago truncatula/metabolismo , Medicago truncatula/genética , Medicago truncatula/crescimento & desenvolvimento , Pulvínulo/metabolismo , Movimento , Água/metabolismo , Regulação da Expressão Gênica de Plantas , Mimosa/fisiologia , Mimosa/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
13.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38279209

RESUMO

Sepsis involves an immunological systemic response to a microbial pathogenic insult, leading to a cascade of interconnected biochemical, cellular, and organ-organ interaction networks. Potential drug targets can depict aquaporins, as they are involved in immunological processes. In immune cells, AQP3 and AQP9 are of special interest. In this study, we tested the hypothesis that these aquaporins are expressed in the blood cells of septic patients and impact sepsis survival. Clinical data, routine laboratory parameters, and blood samples from septic patients were analyzed on day 1 and day 8 after sepsis diagnosis. AQP expression and cytokine serum concentrations were measured. AQP3 mRNA expression increased over the duration of sepsis and was correlated with lymphocyte count. High AQP3 expression was associated with increased survival. In contrast, AQP9 expression was not altered during sepsis and was correlated with neutrophil count, and low levels of AQP9 were associated with increased survival. Furthermore, AQP9 expression was an independent risk factor for sepsis lethality. In conclusion, AQP3 and AQP9 may play contrary roles in the pathophysiology of sepsis, and these results suggest that AQP9 may be a novel drug target in sepsis and, concurrently, a valuable biomarker of the disease.


Assuntos
Aquaporinas , Sepse , Humanos , Aquaporina 3/genética , Aquaporina 3/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Sepse/genética
14.
Int J Mol Sci ; 25(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38612752

RESUMO

Excessive sodium intake is associated with nephrolithiasis, but the impact of sodium-deficient (SD) diets is unknown. Hence, we investigated the effects of short- and long-term SD diets on the expression of renal aquaporins and sodium transporters, and thus calcium oxalate (CaOx) crystal formation in hyperoxaluria rats. In a short-term sodium balance study, six male rats received drinking water and six received 0.75% ethylene glycol (EG) to induce hyperoxaluria. After a 30-day period of feeding on normal chow, both groups were treated with a normal-sodium diet for 5 days, followed by a sodium-free diet for the next 5 days. In a long-term SD study (42 days), four groups, induced with EG or not, were treated with normal-sodium water and sodium-free drinking water, alternately. Short-term sodium restriction in EG rats reversed the daily positive sodium balance, but progressively caused a negative cumulative water balance. In the long-term study, the abundant levels of of Na/H exchanger, thiazide-sensitive Na-Cl cotransporter, Na-K-ATPase, and aquaporins-1 from SD + EG rats were markedly reduced, corresponding to a decrease in Uosm, as compared to SD rats. Increased urine calcium, AP(CaOx)index, and renal CaOx deposition were also noted in SD + EG rats. Although the SD treatment reduced sodium excretion, it also increased urinary calcium and impaired renal function, ultimately causing the formation of more CaOx crystals.


Assuntos
Água Potável , Hipercalcemia , Hiperoxalúria , Hiponatremia , Masculino , Animais , Ratos , Sódio , Oxalato de Cálcio , Cálcio , Rim
15.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474310

RESUMO

Obstructive sleep apnea (OSA) is characterized by intermittent repeated episodes of hypoxia-reoxygenation. OSA is associated with cerebrovascular consequences. An enhanced blood-brain barrier (BBB) permeability has been proposed as a marker of those disorders. We studied in mice the effects of 1 day and 15 days intermittent hypoxia (IH) exposure on BBB function. We focused on the dorsal part of the hippocampus and attempted to identify the molecular mechanisms by combining in vivo BBB permeability (Evans blue tests) and mRNA expression of several junction proteins (zona occludens (ZO-1,2,3), VE-cadherin, claudins (1,5,12), cingulin) and of aquaporins (1,4,9) on hippocampal brain tissues. After 15 days of IH exposure we observed an increase in BBB permeability, associated with increased mRNA expressions of claudins 1 and 12, aquaporins 1 and 9. IH seemed to increase early for claudin-1 mRNA expression as it doubled with 1 day of exposure and returned near to its base level after 15 days. Claudin-1 overexpression may represent an immediate response to IH exposure. Then, after 15 days of exposure, an increase in functional BBB permeability was associated with enhanced expression of aquaporin. These BBB alterations are possibly associated with a vasogenic oedema that may affect brain functions and accelerate neurodegenerative processes.


Assuntos
Aquaporinas , Apneia Obstrutiva do Sono , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , Claudina-1/metabolismo , Modelos Animais de Doenças , Hipóxia/metabolismo , Claudinas/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Permeabilidade , Aquaporinas/metabolismo , RNA Mensageiro/metabolismo , Claudina-5/metabolismo
16.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892245

RESUMO

Breeding salt-tolerant crops is necessary to reduce food insecurity. Prebreeding populations are fundamental for uncovering tolerance alleles from wild germplasm. To obtain a physiological interpretation of the agronomic salt tolerance and better criteria to identify candidate genes, quantitative trait loci (QTLs) governing productivity-related traits in a population of recombinant inbred lines (RIL) derived from S. pimpinellifolium were reanalyzed using an SNP-saturated linkage map and clustered using QTL meta-analysis to synthesize QTL information. A total of 60 out of 85 QTLs were grouped into 12 productivity MQTLs. Ten of them were found to overlap with other tomato yield QTLs that were found using various mapping populations and cultivation conditions. The MQTL compositions showed that fruit yield was genetically associated with leaf water content. Additionally, leaf Cl- and K+ contents were related to tomato productivity under control and salinity conditions, respectively. More than one functional candidate was frequently found, explaining most productivity MQTLs, indicating that the co-regulation of more than one gene within those MQTLs might explain the clustering of agronomic and physiological QTLs. Moreover, MQTL1.2, MQTL3 and MQTL6 point to the root as the main organ involved in increasing productivity under salinity through the wild allele, suggesting that adequate rootstock/scion combinations could have a clear agronomic advantage under salinity.


Assuntos
Mapeamento Cromossômico , Locos de Características Quantitativas , Tolerância ao Sal , Solanum , Tolerância ao Sal/genética , Solanum/genética , Solanum/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Melhoramento Vegetal , Ligação Genética , Genes de Plantas
17.
Int J Mol Sci ; 25(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38203778

RESUMO

Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 (Aqp5) knockdown provided enhanced sepsis survival in a murine sepsis model. Potential AQP5 inhibitors provide sulfonamides and their derivatives. In this study, we tested the hypothesis that sulfonamides reduce AQP5 expression in different conditions. The impact of sulfonamides on AQP5 expression and immune cell migration was examined in cell lines REH and RAW 264.7 by qPCR, Western blot and migration assay. Subsequently, whether furosemide and methazolamide are capable of reducing AQP5 expression after LPS incubation was investigated in whole blood samples of healthy volunteers. Incubation with methazolamide (10-5 M) and furosemide (10-6 M) reduced AQP5 mRNA and protein expression by about 30% in REH cells. Pre-incubation of the cells with methazolamide reduced cell migration towards SDF1-α compared to non-preincubated cells to control level. Pre-incubation with methazolamide in PBMCs led to a reduction in LPS-induced AQP5 expression compared to control levels, while furosemide failed to reduce it. Methazolamide appears to reduce AQP5 expression and migration of immune cells. However, after LPS administration, the reduction in AQP5 expression by methazolamide is no longer possible. Hence, our study indicates that methazolamide is capable of reducing AQP5 expression and has the potential to be used in sepsis prophylaxis.


Assuntos
Metazolamida , Sepse , Humanos , Animais , Camundongos , Furosemida , Lipopolissacarídeos , Sulfonamidas , Movimento Celular , Sulfanilamida , Sepse/tratamento farmacológico , RNA Mensageiro/genética , Aquaporina 5/genética
18.
Inflammopharmacology ; 32(2): 1575-1592, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38267609

RESUMO

Aquaporins like AQP1, AQP3, and AQP4 are known to be involved in the pathophysiology of inflammation based on earlier reports. This study aimed to evaluate the involvement of Aquaporins as a potential target of inflammation. The study also investigates the efficacy of methanolic extract of Garcinia (GME) and its potent phytocompound (garcinol) against the Aquaporins involved in inflammation. siRNA silencing of AQP3 was carried out in RAW264.7 cells followed by LPS stimulation (1 µg/ml) and assessment of important markers of inflammation including NO, PGE2, TNF-α, IL-6, IL-1ß, CCL20, iNOS and COX-2. To assess the anti-inflammatory potential of Garcinia extract and garcinol, cells were stimulated with 1 µg/ml LPS in the absence and presence of increasing concentrations of GME and garcinol. During the experimental period, extract concentrations (115 µg/ml and 230 µg/ml for RAW264.7; 118 µg/ml and 236 µg/ml for THP-1) and garcinol concentrations (6 µM and 12 µM for RAW264.7; 3 µM and 6 µM for THP-1) were selected based on the IC50. The anti-inflammatory effects were assessed by measuring the levels of TNF-α, IL-1ß, IL-6, and CCL20 in LPS-stimulated cells. The AQP expression was studied at transcriptional and translational levels using qPCR and Western blot analysis respectively. AQP3 knockdown significantly decreased the NO, PGE2, TNF-α, IL-1ß levels along with iNOS and COX-2 mRNA expression. LPS stimulation led to a significant increase in the mRNA and protein level expression AQP1, AQP3, and AQP4 in RAW264.7 cells; and AQP1 and AQP3 in THP-1 cells indicating their role as markers of inflammation. GME and garcinol effectively suppressed the LPS-induced proinflammatory cytokine production in both cell lines. The results indicate that AQP1, AQP3, and AQP4 could play a crucial role as markers of inflammation. Anti-inflammatory agents like Garcinia could potentially decrease the expression of such AQPs, thus inhibiting the inflammatory process.


Assuntos
Aquaporinas , Terpenos , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Dinoprostona/metabolismo , Ciclo-Oxigenase 2/metabolismo , Lipopolissacarídeos/farmacologia , Interleucina-6/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , RNA Mensageiro/metabolismo
19.
World J Microbiol Biotechnol ; 40(2): 71, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38225445

RESUMO

Because of the hydrophobic nature of the membrane lipid bilayer, the majority of the hydrophilic solutes require special transportation mechanisms for passing through the cell membrane. Integral membrane transport proteins (MTPs), which belong to the Major Intrinsic Protein Family, facilitate the transport of these solutes across cell membranes. MTPs including aquaporins and carrier proteins are transmembrane proteins spanning across the cell membrane. The easy handling of microorganisms enabled the discovery of a remarkable number of transport proteins specific to different substances. It has been realized that these transporters have very important roles in the survival of microorganisms, their pathogenesis, and antimicrobial resistance. Astonishing features related to the solute specificity of these proteins have led to the acceleration of the research on the discovery of their properties and the development of innovative products in which these unique properties are used or imitated. Studies on microbial MTPs range from the discovery and characterization of a novel transporter protein to the mining and screening of them in a large transporter library for particular functions, from simulations and modeling of specific transporters to the preparation of biomimetic synthetic materials for different purposes such as biosensors or filtration membranes. This review presents recent discoveries on microbial membrane transport proteins and focuses especially on formate nitrite transport proteins and aquaporins, and advances in their biotechnological applications.


Assuntos
Aquaporinas , Proteínas de Membrana Transportadoras , Proteínas de Membrana Transportadoras/metabolismo , Membrana Celular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte/metabolismo , Transporte Biológico
20.
Am J Physiol Cell Physiol ; 325(1): C208-C223, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37246634

RESUMO

Cell migration is an essential process that underlies many physiological processes, including the immune response, organogenesis in the embryo, and angiogenesis, as well as pathological processes such as cancer metastasis. Cells have at their disposal a variety of migratory behaviors and mechanisms that seem to be specific to cell type and the microenvironment. Research over the past two decades has elucidated the water channel protein family of aquaporins (AQPs) as a regulator of many cell migration-related processes, from physical phenomena to biological signaling pathways. The roles that AQPs play in cell migration are both cell type- and isoform-specific; thus, a large swath of information has accumulated as researchers seek to identify the responses across these distinct variables. There does not seem to be a universal role that AQPs play in cell migration; the complex interplay between AQPs and cell volume management, signaling pathway activation, and in a few identified circumstances, gene expression regulation, has shown the intricate, and perhaps paradoxical, role of AQPs in cell migration. The objective of this review is to provide an organized and integrated collection of recent work that has elucidated the many mechanisms by which AQPs regulate cell migration.NEW & NOTEWORTHY Research has elucidated the water channel protein family of aquaporins (AQPs) as a regulator of many cell migration-related processes, from physical phenomena to biological signaling pathways. The roles that AQPs play in cell migration are both cell type- and isoform-specific; thus, a large swath of information has accumulated as researchers seek to identify the responses across these distinct variables. This review compiles insights into the recent findings linking AQPs to physiological cell migration.


Assuntos
Aquaporinas , Aquaporinas/genética , Aquaporinas/metabolismo , Regulação da Expressão Gênica , Transdução de Sinais , Movimento Celular
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