Aquaporins

水通道蛋白
  • 文章类型: Journal Article
    三阴性乳腺癌(TNBC)仍然是最具挑战性的亚型之一,因为它最初的特征是缺乏特定的生物标志物和相应的靶向治疗。方法论的进步,翻译信息学,基因组学,和蛋白质组学对治疗靶点的识别做出了重要贡献。创新治疗的发展,如抗体-药物偶联物和免疫检查点抑制剂,除了化疗,现在已经成为护理的标准。然而,对定义治疗结果的生物标志物的探索仍在进行中.过氧化物酶,其中包括一组水通道蛋白,它们是促进水运输的膜孔,甘油,和过氧化氢,已经成为治疗反应的潜在生物标志物。对过氧化物酶的研究表明,它们的参与超出了传统的通道活动,这也反映在它们的细胞定位和在细胞信号通路中的作用。这项关于过氧化物酶的研究为肿瘤治疗抵抗的机制提供了新的见解,为预测治疗结果和定制成功的TNBC疗法提供了潜在的途径。
    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.
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  • 文章类型: Journal Article
    尽管医学不断进步,创伤性脑损伤(TBI)仍然是全球范围内死亡和残疾的主要原因。因此,人们一直在寻求生物标志物,以允许对颅脑外伤后的患者进行非侵入性监测,有可能改善临床管理,降低并发症和死亡率。水通道蛋白(AQP),这对跨膜水运输至关重要,在这种情况下可能很重要。这项研究包括48名患者,其中27例患有急性(aSDH),21例患有慢性硬膜下血肿(cSDH)。以三个间隔从参与者那里收集血浆样本:手术前的第一个样本,第二个在15小时,第三个在手术后30小时。使用夹心ELISA技术测定AQP1,AQP2,AQP4和AQP9的血浆浓度。对所有患者在手术前后进行CT扫描。使用Spearman的非参数等级相关系数检查变量之间的相关性。水通道蛋白2水平与慢性硬膜下血肿体积和中线移位之间存在很强的相关性。然而,在急性硬膜下血肿手术前后,水通道蛋白水平(AQP1、AQP2、AQP4和AQP9)之间没有发现显著联系,慢性硬膜下血肿术后AQP1,AQP4和AQP9也没有。在慢性SDH组中,AQP2血浆浓度与术前测量的中线移位呈负相关(Spearman'sρ-0.54;p=0.017),与基线和术后30h之间的血肿体积变化呈正相关(Spearman'sρ0.627;p=0.007)。急性SDH患者水通道蛋白血浆AQP1、AQP2、AQP4和AQP9水平与血肿体积无统计学相关性。慢性硬膜下血肿体积之间存在相关性,放射学测量,和血清AQP2浓度,强调水通道蛋白作为临床生物标志物的潜力。
    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.
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  • 文章类型: Journal Article
    水通道蛋白(AQP),特别是AQP4,在调节大脑中的流体动力学中起着至关重要的作用,影响创伤性脑损伤(TBI)后水肿的发展和解决。这篇综述探讨了损伤后AQP表达和定位的变化。探讨其对脑水肿和整体损伤结局的影响。我们讨论了调节AQP表达的潜在分子机制,强调调节AQP功能的潜在治疗策略。这些见解提供了对TBI中AQPs的全面理解,并提出了通过有针对性的干预措施改善临床结果的新方法。
    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.
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  • 文章类型: Journal Article
    培育耐盐作物对于减少粮食不安全是必要的。预交种群是从野生种质中发现耐受性等位基因的基础。为了获得农艺耐盐性的生理解释和更好的鉴定候选基因的标准,使用SNP饱和连锁图重新分析了源自木薯的重组自交系(RIL)种群中控制生产力相关性状的数量性状基因座(QTL),并使用QTL荟萃分析进行聚类以合成QTL信息。85个QTL中的60个被分为12个生产率MQTL。发现其中十个与使用各种作图种群和栽培条件发现的其他番茄产量QTL重叠。MQTL组成表明,果实产量与叶片含水量在遗传上相关。此外,在控制和盐度条件下,叶片Cl-和K含量与番茄生产力有关,分别。经常发现不止一个功能候选,解释大多数生产力MQTL,表明这些MQTL中多个基因的共调控可能解释了农艺和生理QTL的聚类。此外,MQTL1.2,MQTL3和MQTL6通过野生等位基因指向根作为参与盐度下生产力提高的主要器官,表明在盐度下,足够的砧木/接穗组合可能具有明显的农艺优势。
    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.
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  • 文章类型: Journal Article
    与气候变化相关的热浪频率和强度的增加会影响葡萄栽培,导致葡萄产量和品质的损失。我们评估了顶篷结构操纵是否可以减轻地中海葡萄园夏季压力的影响。在2019-2020年期间监测了亚历山大植物的葡萄品种马斯喀特。应用了两种冠层射击定位处理:垂直射击定位(VSP)和调制射击定位(MSP)。在MSP中,释放了西侧上部的叶子,以促进部分射击倾斜,遮蔽集群。集群以豌豆大小(PS)采样,veraison(VER),和完全成熟(FM)。测量包括轴解剖和水力导度(Kh)和水通道蛋白(AQP)以及簇组织中与应激相关的基因表达。结果表明,Kh和血管解剖结构存在明显的季节性和年际差异。在VER,rachis和rachis花梗的Kh和木质部直径降低,但不受处理的影响。与VSP相比,MSP的韧皮部-木质部比率增加(2019年)或减少(2020年)。大多数AQP在花梗的FM下调,在牙髓的VER上调。观察到MSP中潜在的成熟变化,并通过所有组织中几种应激相关基因的上调来证实。该研究指出了冠层结构在成熟过程中浆果与水的关系和应激反应中的作用。
    Climate-change-related increases in the frequency and intensity of heatwaves affect viticulture, leading to losses in yield and grape quality. We assessed whether canopy-architecture manipulation mitigates the effects of summer stress in a Mediterranean vineyard. The Vitis vinifera L variety Muscat of Alexandria plants were monitored during 2019-2020. Two canopy shoot-positioning treatments were applied: vertical shoot positioning (VSP) and modulated shoot positioning (MSP). In MSP, the west-side upper foliage was released to promote partial shoot leaning, shading the clusters. Clusters were sampled at pea size (PS), veraison (VER), and full maturation (FM). Measurements included rachis anatomy and hydraulic conductance (Kh) and aquaporins (AQP) and stress-related genes expression in cluster tissues. The results show significant seasonal and interannual differences in Kh and vascular anatomy. At VER, the Kh of the rachis and rachis+pedicel and the xylem diameter decreased but were unaffected by treatments. The phloem-xylem ratio was either increased (2019) or reduced (2020) in MSP compared to VSP. Most AQPs were down-regulated at FM in pedicels and up-regulated at VER in pulp. A potential maturation shift in MSP was observed and confirmed by the up-regulation of several stress-related genes in all tissues. The study pinpoints the role of canopy architecture in berry-water relations and stress response during ripening.
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  • 文章类型: Journal Article
    脂质是膜蛋白结构和功能的关键调节剂。然而,研究蛋白质-脂质相互作用的热力学是具有挑战性的,因为脂质可以同时在不同的位点以不同的特异性结合膜蛋白。这里,我们使用单突变体和双突变体开发了一种天然质谱(MS)方法,以测量水通道蛋白Z(AqpZ)上特定残基对心磷脂(CL)结合的相对能量贡献。我们首先在AqpZ上突变了潜在的脂质结合残基,和混合的突变和野生型蛋白与CL。通过使用天然MS在单一光谱中同时解析与突变体和野生型蛋白的脂质结合,我们直接确定了CL结合的相对亲和力,从而揭示了由突变引起的脂质结合的相对吉布斯自由能变化。比较不同的突变体显示,W14有助于最紧密的CL结合位点,R224有助于较低的亲和力位点。使用双突变循环,我们研究了W14和R224位点对CL结合的协同作用。总的来说,这种新颖的天然MS方法提供了对脂质与膜蛋白特异性位点结合的独特见解。
    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.
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  • 文章类型: Journal Article
    了解大脑和脊髓中流体流动的潜在机制对于发现与中枢神经系统疾病的病理生理学有关的机制至关重要。近年来,研究强调了通过淋巴系统和淋巴网络在大脑中流动的流体的复杂性。关于脊髓中的这些途径知之甚少。流体流动通过淋巴通路的一个重要方面是水通道的作用,特别是水通道蛋白1和4。这篇综述概述了这些水通道蛋白在大脑和脊髓中的作用。并简要介绍健康大脑和脊髓以及创伤性大脑和脊髓损伤期间大脑和脊髓中的液体流动。最后,这篇综述概述了水通道蛋白在创伤性脑和脊髓损伤中的作用,突出了该领域的一些复杂性和知识差距。
    Knowledge about the mechanisms underlying the fluid flow in the brain and spinal cord is essential for discovering the mechanisms implicated in the pathophysiology of central nervous system diseases. During recent years, research has highlighted the complexity of the fluid flow movement in the brain through a glymphatic system and a lymphatic network. Less is known about these pathways in the spinal cord. An important aspect of fluid flow movement through the glymphatic pathway is the role of water channels, especially aquaporin 1 and 4. This review provides an overview of the role of these aquaporins in brain and spinal cord, and give a short introduction to the fluid flow in brain and spinal cord during in the healthy brain and spinal cord as well as during traumatic brain and spinal cord injury. Finally, this review gives an overview of the current knowledge about the role of aquaporins in traumatic brain and spinal cord injury, highlighting some of the complexities and knowledge gaps in the field.
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  • 文章类型: Journal Article
    男性不育上升的原因很多,随着年龄的增长;因此,我们的目的是研究水通道蛋白3、7和8在不同年龄组人类精子中的特征。
    这项研究是针对18岁以上男性的精子样本进行的。共有60名男性被纳入研究,分为三个年龄组:第1组,年龄18-25岁(n=20);第2组,年龄26-35岁(n=20);第3组,年龄≥35岁(n=20)。从每个参与者获得的精子射精用于精子图测试,克鲁格严格的形态学分析,和免疫组织化学。
    我们观察到在宏观和微观精子测试方面没有统计学上的显着差异。水通道蛋白-3的免疫染色评分在组1中最低,在组3和组2中分别升高(p<0.05)。水通道蛋白-8免疫染色仅在第2组中增加(p<0.05)。水通道蛋白-7免疫染色评分在各组间无差异(p>0.05)。当将水通道蛋白分子的免疫染色评分相互比较时,水通道蛋白-7与其他蛋白相比显著增加(p<0.05)。
    根据结果,可以说,水通道蛋白-3和水通道蛋白-8分子在26至35岁时表达更多,水通道蛋白-7在18至25岁时密集表达。如果这些分子的表征受到不利影响,男性不育最终可能会出现。我们建议对这一主题进行进一步的高级研究。
    UNASSIGNED: 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.
    UNASSIGNED: 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.
    UNASSIGNED: 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).
    UNASSIGNED: 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.
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  • 文章类型: Journal Article
    叶片运动是植物响应内外环境变化的一种表现,旨在优化植物的生长发育。叶片运动通常由专门的运动器官驱动,Pulvinus,这种运动与牙髓两侧的体积和膨胀的不同变化有关。蓝光,生长素,GA,H+-ATP酶,K+,Cl-,Ca2+,肌动蛋白,和水通道蛋白共同影响肺伸肌和屈肌组织的水通量变化,以建立膨胀压差,从而控制叶片的运动。然而,这些因素如何调节一个物种中的髓组织的多细胞运动性仍然不清楚。此外,模型植物,如苜蓿,含羞草,和SamaneaSaman被用来研究pulvinus驱动的叶片运动,显示出它们的脉搏运动机制相似。在这次审查中,我们总结了三个模型工厂过去的研究成果,以Medicagotruncatula为例,表明调节pulvinus运动的基因也参与调节植物的生长和发育。我们还提出了一个模型,其中离子通量和水通量的变化是脉冲运动的关键步骤,并突出了未来研究的问题。
    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.
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  • 文章类型: Journal Article
    快速的集体运动广泛存在于生物分子中,但它们的功能相关性仍不清楚。在这里,通过使用固态核磁共振(ssNMR)光谱和分子动力学(MD)模拟,我们发现骨架的快速集体运动对于水通道蛋白Z(AqpZ)的水转移至关重要。通过结合13C和1H检测的多维ssNMR光谱,测量了主链的总共212个残基位点特异性偶极有序参数和158个15N自旋弛豫速率。通过理论模型对这些实验数据的分析表明,跨膜α螺旋在纳秒至微秒时间尺度上的小振幅(〜10°)集体运动对于AqpZ的动力学是主要的。MD模拟表明,这些集体运动对AqpZ的水传递效率至关重要,因为它可以促进通道的打开并加速选择性过滤区域中的水-残留氢键的更新。
    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.
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