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1.
J Physiol ; 602(13): 3003-3005, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38896793
2.
Physiol Plant ; 176(3): e14384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859697

RESUMO

The present study aims to explore the potential of a plasma-membrane localized PIP2-type aquaporin protein sourced from the halophyte Salicornia brachiata to alleviate salinity and water deficit stress tolerance in a model plant through transgenic intervention. Transgenic plants overexpressing SbPIP2 gene showed improved physio-biochemical parameters like increased osmolytes (proline, total sugar, and amino acids), antioxidants (polyphenols), pigments and membrane stability under salinity and drought stresses compared to control plants [wild type (WT) and vector control (VC) plants]. Multivariate statistical analysis showed that, under water and salinity stresses, osmolytes, antioxidants and pigments were correlated with SbPIP2-overexpressing (SbPIP2-OE) plants treated with salinity and water deficit stress, suggesting their involvement in stress tolerance. As aquaporins are also involved in CO2 transport, SbPIP2-OE plants showed enhanced photosynthesis performance than wild type upon salinity and drought stresses. Photosynthetic gas exchange (net CO2 assimilation rate, PSII efficiency, ETR, and non-photochemical quenching) were significantly higher in SbPIP2-OE plants compared to control plants (wild type and vector control plants) under both unstressed and stressed conditions. The higher quantum yield for reduction of end electron acceptors at the PSI acceptor side [Φ( R0 )] in SbPIP2-OE plants compared to control plants under abiotic stresses indicates a continued PSI functioning, leading to retained electron transport rate, higher carbon assimilation, and less ROS-mediated injuries. In conclusion, the SbPIP2 gene functionally validated in the present study could be a potential candidate for engineering abiotic stress resilience in important crops.


Assuntos
Secas , Nicotiana , Fotossíntese , Proteínas de Plantas , Plantas Geneticamente Modificadas , Estresse Fisiológico , Fotossíntese/genética , Nicotiana/genética , Nicotiana/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Chenopodiaceae/genética , Chenopodiaceae/fisiologia , Chenopodiaceae/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Salinidade , Regulação da Expressão Gênica de Plantas , Antioxidantes/metabolismo
3.
Int J Mol Sci ; 25(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38928258

RESUMO

Aquaporins (AQPs), particularly AQP4, play a crucial role in regulating fluid dynamics in the brain, impacting the development and resolution of edema following traumatic brain injury (TBI). This review examines the alterations in AQP expression and localization post-injury, exploring their effects on brain edema and overall injury outcomes. We discuss the underlying molecular mechanisms regulating AQP expression, highlighting potential therapeutic strategies to modulate AQP function. These insights provide a comprehensive understanding of AQPs in TBI and suggest novel approaches for improving clinical outcomes through targeted interventions.


Assuntos
Aquaporinas , Lesões Encefálicas Traumáticas , Lesões Encefálicas Traumáticas/metabolismo , Humanos , Animais , Aquaporinas/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/etiologia , Aquaporina 4/metabolismo , Hidrodinâmica , Encéfalo/metabolismo
4.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38928322

RESUMO

Despite continuous medical advancements, traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Consequently, there is a pursuit for biomarkers that allow non-invasive monitoring of patients after cranial trauma, potentially improving clinical management and reducing complications and mortality. Aquaporins (AQPs), which are crucial for transmembrane water transport, may be significant in this context. This study included 48 patients, with 27 having acute (aSDH) and 21 having chronic subdural hematoma (cSDH). Blood plasma samples were collected from the participants at three intervals: the first sample before surgery, the second at 15 h, and the third at 30 h post-surgery. Plasma concentrations of AQP1, AQP2, AQP4, and AQP9 were determined using the sandwich ELISA technique. CT scans were performed on all patients pre- and post-surgery. Correlations between variables were examined using Spearman's nonparametric rank correlation coefficient. A strong correlation was found between aquaporin 2 levels and the volume of chronic subdural hematoma and midline shift. However, no significant link was found between aquaporin levels (AQP1, AQP2, AQP4, and AQP9) before and after surgery for acute subdural hematoma, nor for AQP1, AQP4, and AQP9 after surgery for chronic subdural hematoma. In the chronic SDH group, AQP2 plasma concentration negatively correlated with the midline shift measured before surgery (Spearman's ρ -0.54; p = 0.017) and positively with hematoma volume change between baseline and 30 h post-surgery (Spearman's ρ 0.627; p = 0.007). No statistically significant correlation was found between aquaporin plasma levels and hematoma volume for AQP1, AQP2, AQP4, and AQP9 in patients with acute SDH. There is a correlation between chronic subdural hematoma volume, measured radiologically, and serum AQP2 concentration, highlighting aquaporins' potential as clinical biomarkers.


Assuntos
Aquaporina 2 , Biomarcadores , Edema Encefálico , Humanos , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Idoso , Prognóstico , Edema Encefálico/sangue , Edema Encefálico/etiologia , Edema Encefálico/diagnóstico por imagem , Aquaporina 2/sangue , Aquaporina 2/metabolismo , Adulto , Traumatismos Craniocerebrais/sangue , Traumatismos Craniocerebrais/complicações , Hematoma Subdural Crônico/sangue , Hematoma Subdural Crônico/cirurgia , Aquaporina 1/sangue , Aquaporina 1/metabolismo , Tomografia Computadorizada por Raios X , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/diagnóstico , Aquaporinas/sangue , Aquaporinas/metabolismo
5.
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
6.
Anal Chem ; 96(25): 10426-10433, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38859611

RESUMO

Lipids are critical modulators of membrane protein structure and function. However, it is challenging to investigate the thermodynamics of protein-lipid interactions because lipids can simultaneously bind membrane proteins at different sites with different specificities. Here, we developed a native mass spectrometry (MS) approach using single and double mutants to measure the relative energetic contributions of specific residues on Aquaporin Z (AqpZ) toward cardiolipin (CL) binding. We first mutated potential lipid-binding residues on AqpZ, and mixed mutant and wild-type proteins together with CL. By using native MS to simultaneously resolve lipid binding to the mutant and wild-type proteins in a single spectrum, we directly determined the relative affinities of CL binding, thereby revealing the relative Gibbs free energy change for lipid binding caused by the mutation. Comparing different mutants revealed that W14 contributes to the tightest CL binding site, with R224 contributing to a lower affinity site. Using double mutant cycling, we investigated the synergy between W14 and R224 sites on CL binding. Overall, this novel native MS approach provides unique insights into the binding of lipids to specific sites on membrane proteins.


Assuntos
Aquaporinas , Cardiolipinas , Espectrometria de Massas , Mutação , Cardiolipinas/química , Cardiolipinas/metabolismo , Aquaporinas/química , Aquaporinas/metabolismo , Aquaporinas/genética , Sítios de Ligação , Ligação Proteica , Proteínas de Membrana/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/genética , Termodinâmica , Modelos Moleculares , Proteínas de Escherichia coli
7.
Hum Cell ; 37(4): 917-930, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38806940

RESUMO

Aquaporins (AQPs) are small, integral proteins facilitating water transport across plasma cell membranes in response to osmotic gradients. This family has 13 unique members (AQP0-12), which can also transport glycerol, urea, gases, and other salute small molecules. AQPs play a crucial role in the regulation of different cellular processes, including metabolism, migration, immunity, barrier function, and angiogenesis. These proteins are found to aberrantly overexpress in various cancers, including colorectal cancer (CRC). Growing evidence has explored AQPs as a potential diagnostic biomarker and therapeutic target in different cancers. However, there is no comprehensive review compiling the available information on the crucial role of AQPs in the context of colorectal cancer. This review highlights the significance of AQPs as the biomarker and regulator of tumor cells metabolism. In addition, the proliferation, angiogenesis, and metastasis of tumor cells related to AQPs expression as well as function are discussed. Understanding the AQPs prominent role in chemotherapy resistance is of great importance clinically.


Assuntos
Aquaporinas , Carcinogênese , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Metástase Neoplásica , Neovascularização Patológica , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Aquaporinas/metabolismo , Aquaporinas/fisiologia , Carcinogênese/metabolismo , Carcinogênese/genética , Resistencia a Medicamentos Antineoplásicos/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Expressão Gênica/genética , Terapia de Alvo Molecular
8.
New Phytol ; 243(1): 195-212, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38708439

RESUMO

Water plays crucial roles in expeditious growth and osmotic stress of bamboo. Nevertheless, the molecular mechanism of water transport remains unclear. In this study, an aquaporin gene, PeTIP4-3, was identified through a joint analysis of root pressure and transcriptomic data in moso bamboo (Phyllostachys edulis). PeTIP4-3 was highly expressed in shoots, especially in the vascular bundle sheath cells. Overexpression of PeTIP4-3 could increase drought and salt tolerance in transgenic yeast and rice. A co-expression pattern of PeSAPK4, PeMYB99 and PeTIP4-3 was revealed by WGCNA. PeMYB99 exhibited an ability to independently bind to and activate PeTIP4-3, which augmented tolerance to drought and salt stress. PeSAPK4 could interact with and phosphorylate PeMYB99 in vivo and in vitro, wherein they synergistically accelerated PeTIP4-3 transcription. Overexpression of PeMYB99 and PeSAPK4 also conferred drought and salt tolerance in transgenic rice. Further ABA treatment analysis indicated that PeSAPK4 enhanced water transport in response to stress via ABA signaling. Collectively, an ABA-mediated cascade of PeSAPK4-PeMYB99-PeTIP4-3 is proposed, which governs water transport in moso bamboo.


Assuntos
Aquaporinas , Secas , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Plantas Geneticamente Modificadas , Água , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Água/metabolismo , Oryza/genética , Oryza/metabolismo , Oryza/fisiologia , Aquaporinas/metabolismo , Aquaporinas/genética , Transporte Biológico , Poaceae/genética , Poaceae/fisiologia , Modelos Biológicos , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Tolerância ao Sal/genética , Fosforilação , Ligação Proteica/efeitos dos fármacos , Estresse Fisiológico
9.
Cancer Invest ; 42(4): 345-356, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742677

RESUMO

BACKGROUND: Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. MATERIALS AND METHODS: We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. RESULT: We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. CONCLUSIONS: This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas.


Assuntos
Aquaporinas , Proliferação de Células , Glioma , Peróxido de Hidrogênio , Mitocôndrias , Espécies Reativas de Oxigênio , Humanos , Mitocôndrias/metabolismo , Glioma/metabolismo , Glioma/patologia , Glioma/genética , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Aquaporinas/metabolismo , Aquaporinas/genética , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Transdução de Sinais
10.
Sci Adv ; 10(19): eade9520, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38718112

RESUMO

Fast collective motions are widely present in biomolecules, but their functional relevance remains unclear. Herein, we reveal that fast collective motions of backbone are critical to the water transfer of aquaporin Z (AqpZ) by using solid-state nuclear magnetic resonance (ssNMR) spectroscopy and molecular dynamics (MD) simulations. A total of 212 residue site-specific dipolar order parameters and 158 15N spin relaxation rates of the backbone are measured by combining the 13C- and 1H-detected multidimensional ssNMR spectra. Analysis of these experimental data by theoretic models suggests that the small-amplitude (~10°) collective motions of the transmembrane α helices on the nanosecond-to-microsecond timescales are dominant for the dynamics of AqpZ. The MD simulations demonstrate that these collective motions are critical to the water transfer efficiency of AqpZ by facilitating the opening of the channel and accelerating the water-residue hydrogen bonds renewing in the selectivity filter region.


Assuntos
Aquaporinas , Simulação de Dinâmica Molecular , Água , Água/química , Aquaporinas/química , Aquaporinas/metabolismo , Conformação Proteica em alfa-Hélice , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Ressonância Magnética Nuclear Biomolecular , Proteínas de Escherichia coli
11.
Cryo Letters ; 45(3): 158-167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709187

RESUMO

BACKGROUND: Aquaporins (AQPs) are essential proteins that facilitate the rapid movement of water and cryoprotective agents (CPAs) during the cryopreservation process, and ensure the cryo-tolerance of sperm cells. OBJECTIVE: This study evaluated the preservation of aquaporin levels in human sperm after undergoing freezing using natural deep eutectic solvents (NADES) as CPAs for cryoprotection. MATERIALS AND METHODS: From June 2021 to October 2022, 35 semen samples with normal sperm parameters were acquired from the Mehr Infertility Treatment Institute in Rasht, Iran. The samples were divided into several groups for analysis: control group (not frozen), group frozen with SpermFreeze Solution, and groups frozen with different NADESs, including ChS, ChX, ChU, ChG, GlyP, and EtP. After thawing, various aspects for each group were assessed, including the integrity and condensation of sperm chromatin, viability, motility, integrity of acrosome, and the expression of AQP1, AQP3, AQP7, AQP8, and AQP9 genes. RESULTS: The analysis of gene expression revealed that freezing with ChS and GlyP preserved the expression of the AQP1 and AQP3 genes compared to the control group. Regarding AQP7 and AQP8, significant differences were not observed in expression levels between certain NADES groups (e.g., ChS, ChU, and GlyP) and the control group. Additionally, samples frozen with specific NADESs, such as ChS, ChG, EtP, and GlyP, exhibited preserved levels of AQP9 expression when compared to the control group. CONCLUSION: These findings emphasize the importance of NADES in preserving the expression of aquaporins in cryopreserved human sperm and their important fertility parameters. Doi.org/10.54680/fr24310110512.


Assuntos
Aquaporinas , Criopreservação , Crioprotetores , Preservação do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Humanos , Masculino , Criopreservação/métodos , Aquaporinas/genética , Aquaporinas/metabolismo , Espermatozoides/metabolismo , Espermatozoides/efeitos dos fármacos , Crioprotetores/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Preservação do Sêmen/métodos , Solventes/química , Adulto , Sobrevivência Celular/efeitos dos fármacos
12.
Turk J Med Sci ; 54(1): 204-212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812647

RESUMO

Background/aim: Male infertility rises for many reasons, along with age; therefore, we aimed to research the characterization of aquaporin-3, 7, and 8 in human sperm belonging to different age groups. Material and methods: This study was conducted on sperm samples of men aged over 18 years. A total of 60 men were included in the study and divided into three age groups: group 1, age 18-25 years (n = 20); group 2, age 26-35 years (n = 20); and group 3, age ≥35 years (n = 20). Sperm ejaculates obtained from each participant were used for spermiogram tests, Kruger strict morphology analysis, and immunohistochemistry. Results: We observed no statistically significant differences in terms of macroscopic and microscopic sperm testing. The immunostaining score of aquaporin-3 was the lowest in group 1 and increased in group 3 and group 2, respectively (p < 0.05). Aquaporin-8 immunostaining only increased in group 2 (p < 0.05). Aquaporin-7 immunostaining scores were not different between the groups (p > 0.05). When the immunostaining scores of aquaporin molecules were compared with each other, aquaporin-7 was significantly increased compared with the others (p < 0.05). Conclusion: According to the results, it can be stated that aquaporin-3 and aquaporin-8 molecules were more expressed at age 26 to 35 years, and aquaporin-7 was densely expressed from age 18 to 25 years. If the characterization of these molecules is adversely affected, male infertility may eventually emerge. We recommend further advanced-level studies on this subject.


Assuntos
Aquaporina 3 , Aquaporinas , Espermatozoides , Humanos , Masculino , Adulto , Aquaporinas/metabolismo , Aquaporinas/análise , Espermatozoides/metabolismo , Adulto Jovem , Adolescente , Aquaporina 3/metabolismo , Aquaporina 3/análise , Infertilidade Masculina/metabolismo , Fatores Etários , Imuno-Histoquímica , Análise do Sêmen/métodos
13.
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
14.
Plant Cell Rep ; 43(4): 110, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564104

RESUMO

KEY MESSAGE: Nanoparticle pretreatment improved the health of aged Cajanus cajan seeds viz., regulation of redox status, gene expression, and restoration of hormonal homeostasis. Ageing deteriorates the quality of seeds by lowering their vigor and viability, and terminating with loss of germination. These days, nanotechnology has been seen to revolutionize the agricultural sectors, and particularly nano zinc oxide (nZnO) has gained considerable interests due to its distinctive properties. The aim of the present work was to decipher the possibilities of using nZnO to rejuvenate accelerated aged (AA) seeds of Cajanus cajan. Both chemically (CnZnO) and green (GnZnO; synthesized using Moringa oleifera) fabricated nZnOs were characterized via standard techniques to interpret their purity, size, and shape. Experimental results revealed erratic germination with a decline in viability and membrane stability as outcomes of reactive oxygen intermediate (ROI) buildup in AA seeds. Application of nZnO substantially rebated the accrual of ROI, along with enhanced production of antioxidants, α-amylase activity, total sugar, protein and DNA content. Higher level of zinc was assessed qualitatively/ histologically and quantitatively in nZnO pulsed AA seeds, supporting germination without inducing toxicity. Meantime, augmentation in the gibberellic acid with a simultaneous reduction in the abscisic acid level were noted in nZnO invigorated seeds than that determined in the AA seeds, suggesting possible involvement of ROI in hormonal signalling. Furthermore, nZnO-subjected AA seeds unveiled differential expression of aquaporins and cell cycle regulatory genes. Summarizing, among CnZnO and GnZnO, later one holds better potential for a revival of AA seeds of Cajanus cajan by providing considerable tolerance against ageing-associated deterioration via recouping the cellular redox homeostasis, hormonal signaling, and alteration in expression patterns of aquaporin and cell cycle regulatory genes.


Assuntos
Aquaporinas , Cajanus , Óxido de Zinco , Óxido de Zinco/farmacologia , Genes Reguladores , Ciclo Celular
15.
Alzheimers Dement ; 20(6): 3839-3851, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38629888

RESUMO

INTRODUCTION: Age-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes. METHODS: Brain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants who came to autopsy underwent post mortem (PM) 7 tesla MRI with targeted histopathological sampling of WMHs and NAWM. Stained slides were digitized and quantified. Mixed-effects models determined differences in molecular characteristics between WMHs and the NAWM and across NAWM. RESULTS: PM MRI-targeted WMHs are characterized by demyelination, microglial activation, and prominent astrocytic alterations, including disrupted aquaporin (AQP) expression. Similar changes occur within the surrounding NAWM in a pattern of decreasing severity with increased distance from WMHs. DISCUSSION: Decreased AQP expression within WMH and proximal NAWM suggest an overwhelmed system wherein water homeostasis is no longer maintained, contributing to WM damage in older individuals. HIGHLIGHTS: Post mortem magnetic resonance imaging (MRI) was used to characterize the pathology of white matter hyperintensities (WMHs) and surrounding normal appearing white matter (NAWM). Stained immunohistochemical (IHC) slides from targeted WMH and NAWM samples were digitized and quantified. WMHs and NAWM were associated with inflammation, demyelination, and gliosis. WMHs and NAWM astrocytic changes included decreased AQP1 and AQP4 expression. Abnormal NAWM pathology diminished in severity with increasing distance from WMH.


Assuntos
Imageamento por Ressonância Magnética , Substância Branca , Humanos , Substância Branca/patologia , Substância Branca/diagnóstico por imagem , Idoso de 80 Anos ou mais , Feminino , Masculino , Encéfalo/patologia , Aquaporinas/metabolismo , Astrócitos/patologia , Astrócitos/metabolismo , Autopsia , Envelhecimento/patologia , Idoso , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo
16.
J Hazard Mater ; 471: 134325, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38643573

RESUMO

Arsenic (As) contamination in rice poses a significant threat to human health due to its toxicity and widespread consumption. Identifying and manipulating key genes governing As accumulation in rice is crucial for reducing this threat. The large NIP gene family of aquaporins in rice presents a promising target due to functional redundancy, potentially allowing for gene manipulation without compromising plant growth. This study aimed to utilize genome editing to generate knock-out (KO) lines of genes of NIP family (OsLsi1, OsNIP3;1) and an anion transporter family (OsLsi2), in order to assess their impact on As accumulation and stress tolerance in rice. KO lines were created using CRISPR/Cas9 technology, and the As accumulation patterns, physiological performance, and grain yield were compared against wild-type (WT) under As-treated conditions. KO lines exhibited significantly reduced As accumulation in grain compared to WT. Notably, Osnip3;1 KO line displayed reduced As in xylem sap (71-74%) and grain (32-46%) upon treatment. Additionally, these lines demonstrated improved silicon (23%) uptake, photosynthetic pigment concentrations (Chl a: 77%; Chl b: 79%, Total Chl: 79% & Carotenoid: 49%) overall physiological and agronomical performance under As stress compared to WT. This study successfully utilized genome editing for the first time to identify OsNIP3;1 as a potential target for manipulating As accumulation in rice without compromising grain yield or plant vigor.


Assuntos
Arsênio , Sistemas CRISPR-Cas , Edição de Genes , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Arsênio/metabolismo , Arsênio/toxicidade , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Técnicas de Inativação de Genes , Silício/metabolismo , Plantas Geneticamente Modificadas/genética , Clorofila/metabolismo
17.
Phytomedicine ; 129: 155593, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38621329

RESUMO

BACKGROUND: Preventing joint edema is crucial in halting osteoarthritis (OA) progression. Growing clinical evidence indicate that Jianpi-Tongluo Formula (JTF) may have a promising anti-edema effect. However, the therapeutic properties of JTF and the underlying mechanisms remains unclear. MATERIALS AND METHODS: An OA rat model was established and employed to evaluate pharmacological effects of JTF in vivo based on dynamic histopathologic assessments and micro-CT observations. Then, OA-related genes and potential targets of JTF were identified through clinical transcriptomic data analysis and "disease gene-drug target" network analysis, which were verified by a series of in vivo experiments. RESULTS: JTF administration effectively reduced pain and joint edema, inhibited matrix degradation, chondrocyte apoptosis, and aquaporin expression in OA rats. Notably, JTF dose-dependently reversed damage-associated molecular patterns and inflammatory factor upregulation. Mechanically, our "disease gene-drug target" network analysis indicated that the NCOA4-HMGB1-GSK3B-AQPs axis, implicated in ferroptosis and aquaporin dysregulation, may be potentially served as a target of JTF against OA. Accordingly, JTF mitigated NCOA4, HMGB1, and GSK3B expression, oxidative stress, and iron metabolism aberrations in OA rats. Furthermore, JTF treatment significantly attenuated the aberrant upregulation of AQP1, AQP3, and AQP4 proteins observed in cartilage tissues of OA rats. CONCLUSION: Our data reveal for the first time that JTF may exert cartilage protective and anti-edema effects in osteoarthritis therapy by inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.


Assuntos
Ferroptose , Proteína HMGB1 , Osteoartrite , Ratos Sprague-Dawley , Animais , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Ferroptose/efeitos dos fármacos , Ratos , Masculino , Proteína HMGB1/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Edema/tratamento farmacológico , Aquaporinas/metabolismo , Coativadores de Receptor Nuclear/metabolismo , Modelos Animais de Doenças , Aquaporina 3/metabolismo , Aquaporina 1/metabolismo
18.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38673792

RESUMO

Arbuscular mycorrhizal fungi symbiosis plays important roles in enhancing plant tolerance to biotic and abiotic stresses. Aquaporins have also been linked to improved drought tolerance in plants and the regulation of water transport. However, the mechanisms that underlie this association remain to be further explored. In this study, we found that arbuscular mycorrhiza fungi symbiosis could induce the gene expression of the aquaporin ZmTIP2;3 in maize roots. Moreover, compared with the wild-type plants, the maize zmtip2;3 mutant also showed a lower total biomass, colonization rate, relative water content, and POD and SOD activities after arbuscular mycorrhiza fungi symbiosis under drought stress. qRT-PCR assays revealed reduced expression levels of stress genes including LEA3, P5CS4, and NECD1 in the maize zmtip2;3 mutant. Taken together, these data suggest that ZmTIP2;3 plays an important role in promoting maize tolerance to drought stress during arbuscular mycorrhiza fungi symbiosis.


Assuntos
Aquaporinas , Secas , Regulação da Expressão Gênica de Plantas , Micorrizas , Proteínas de Plantas , Simbiose , Zea mays , Zea mays/microbiologia , Zea mays/genética , Zea mays/metabolismo , Micorrizas/fisiologia , Simbiose/genética , Aquaporinas/metabolismo , Aquaporinas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Resistência à Seca
19.
Rev Alerg Mex ; 71(1): 56, 2024 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-38683074

RESUMO

OBJECTIVE: Conduct an in-silico assessment of potential molecular mimicry between human aquaporins, A. fumigatus, and diverse allergenic sources. METHODS: Amino acid sequences of human AQP3 and A. fumigatus aquaporin were compared through multiple alignments with 25 aquaporins from diverse allergenic sources. Phylogenetic analysis and homology-based modeling were executed, and the ElliPro server predicted conserved antigenic regions on 3D structures. RESULTS: Global identity among studied aquaporins was 32.6%, with a specific conserved local region at 71.4%. Five monophyletic clades (A-E) were formed, and Group B displayed the highest identity (95%), including 6 mammalian aquaporins, notably AQP3. A. fumigatus aquaporin exhibited the highest identity with Malassezia sympodialis (35%). Three linear and three discontinuous epitopes were identified in both human and A. fumigatus aquaporins. The Root Mean Square Deviation (RMSD) from overlapping aquaporin structures was 1.006. CONCLUSION: Identification of potential linear and conformational epitopes on human AQP3 suggests likely molecular mimicry with A. fumigatus aquaporins. High identity in a specific antigenic region indicates potential autoreactivity and a probable antigenic site involved in cross-reactivity. Validation through in vitro and in vivo studies is essential for further understanding and confirmation.


OBJETIVO: Realizar una evaluación in silico del posible mimetismo molecular entre las acuaporinas humanas, A. fumigatus y diversas fuentes alergénicas. MÉTODOS: Se compararon secuencias de aminoácidos de AQP3 humana y acuaporina de A. fumigatus mediante alineamientos múltiples con 25 acuaporinas de diversas fuentes alergénicas. Se ejecutaron análisis filogenéticos y modelos basados en homología, y el servidor ElliPro predijo regiones antigénicas preservadas en estructuras 3D. RESULTADOS: La identidad global entre las acuaporinas estudiadas fue del 32.6%, con una región local específica preservada en el 71.4%. Se formaron cinco clados monofiléticos (A-E), y el grupo B mostró la identidad más alta (95%), incluidas 6 acuaporinas de mamíferos, en particular AQP3. A. fumigatus aquaporin exhibió la mayor identidad con Malassezia sympodialis (35%). Se identificaron tres epítopos lineales y tres discontinuos en acuaporinas tanto humanas como de A. fumigatus. La desviación cuadrática media (RMSD) de las estructuras de acuaporinas superpuestas fue de 1,006. CONCLUSIÓN: La identificación de posibles epítopos lineales y conformacionales en AQP3 humano sugiere un probable mimetismo molecular con acuaporinas de A. fumigatus. La identidad alta en una región antigénica específica indica autorreactividad potencial y un sitio antigénico probable implicado en la reactividad cruzada. La validación mediante estudios in vitro e in vivo es desicivo para una mayor comprensión y confirmación.


Assuntos
Alérgenos , Aquaporina 3 , Aquaporinas , Aspergillus fumigatus , Simulação por Computador , Mimetismo Molecular , Aspergillus fumigatus/imunologia , Humanos , Aquaporinas/química , Aquaporinas/genética , Aquaporinas/metabolismo , Aquaporinas/imunologia , Aquaporina 3/metabolismo , Aquaporina 3/genética , Alérgenos/imunologia , Hipersensibilidade/imunologia , Proteínas Fúngicas/química , Proteínas Fúngicas/imunologia , Proteínas Fúngicas/genética , Sequência de Aminoácidos , Filogenia , Epitopos/imunologia
20.
J Mol Med (Berl) ; 102(6): 773-785, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38668786

RESUMO

Autosomal dominant polycystic kidney disease is a genetic kidney disease caused by mutations in the genes PKD1 or PKD2. Its course is characterized by the formation of progressively enlarged cysts in the renal tubules bilaterally. The basic genetic explanation for autosomal dominant polycystic kidney disease is the double-hit theory, and many of its mechanistic issues can be explained by the cilia doctrine. However, the precise molecular mechanisms underpinning this condition's occurrence are still not completely understood. Experimental evidence suggests that aquaporins, a class of transmembrane channel proteins, including aquaporin-1, aquaporin-2, aquaporin-3, and aquaporin-11, are involved in the mechanism of autosomal dominant polycystic kidney disease. Aquaporins are either a potential new target for the treatment of autosomal dominant polycystic kidney disease, and further study into the physiopathological role of aquaporins in autosomal dominant polycystic kidney disease will assist to clarify the disease's pathophysiology and increase the pool of potential treatment options. We primarily cover pertinent findings on aquaporins in autosomal dominant polycystic kidney disease in this review.


Assuntos
Aquaporinas , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/metabolismo , Rim Policístico Autossômico Dominante/genética , Aquaporinas/metabolismo , Aquaporinas/genética , Animais , Mutação
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