ion homeostasis

离子稳态
  • 文章类型: Journal Article
    受盐影响的土地的全球扩张是一个重要因素,限制作物的生长和产量,特别是水稻(水稻)。本实验探讨了在施用植物生长促进根际细菌(PGPR)后减轻水稻(cvBRRIdhan100)中盐引起的损害。
    水稻幼苗,移植后五到六周,以7天的间隔使用50和100mMNaCl进行盐胁迫处理。由内生PGPR(枯草芽孢杆菌和B.aryabhattai)和附生PGPR(B.aryabhattai)在三个关键阶段进行:移植42天大的幼苗,移植后五周的营养阶段,移植后7周的穗起始阶段。
    盐胁迫诱导的渗透胁迫,离子失衡,和水稻植株的氧化损伤,从而对增长产生负面影响,光合效率降低,和荷尔蒙调节的变化,随着甲基乙二醛(MG)毒性增加。PGPR处理通过改善植物抗氧化防御能力来减轻盐度效应,恢复离子平衡,加强水平衡,增加营养吸收,改善光合属性,促进激素合成,和增强MG排毒。
    这些发现强调了PGPR通过作为盐胁迫诱导的损伤的有效缓冲来增强水稻生理和生化功能的潜力。枯草芽孢杆菌表现出最大的好处,而内生和附生的B.aryabhattai在减轻盐胁迫引起的水稻植物损伤方面都具有值得称赞的作用。
    UNASSIGNED: The ongoing global expansion of salt-affected land is a significant factor, limiting the growth and yield of crops, particularly rice (Oryza sativa L). This experiment explores the mitigation of salt-induced damage in rice (cv BRRI dhan100) following the application of plant growth-promoting rhizobacteria (PGPR).
    UNASSIGNED: Rice seedlings, at five- and six-weeks post-transplanting, were subjected to salt stress treatments using 50 and 100 mM NaCl at seven-day intervals. Bacterial cultures consisting of endophytic PGPR (Bacillus subtilis and B. aryabhattai) and an epiphytic PGPR (B. aryabhattai) were administered at three critical stages: transplantation of 42-day-old seedlings, vegetative stage at five weeks post-transplantation, and panicle initiation stage at seven weeks post-transplantation.
    UNASSIGNED: Salt stress induced osmotic stress, ionic imbalances, and oxidative damage in rice plants, with consequent negative effects on growth, decrease in photosynthetic efficiency, and changes in hormonal regulation, along with increased methylglyoxal (MG) toxicity. PGPR treatment alleviated salinity effects by improving plant antioxidant defenses, restoring ionic equilibrium, enhancing water balance, increasing nutrient uptake, improving photosynthetic attributes, bolstering hormone synthesis, and enhancing MG detoxification.
    UNASSIGNED: These findings highlight the potential of PGPR to bolster physiological and biochemical functionality in rice by serving as an effective buffer against salt stress-induced damage. B. subtilis showed the greatest benefits, while both the endophytic and epiphytic B. aryabhattai had commendable effects in mitigating salt stress-induced damage in rice plants.
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  • 文章类型: Journal Article
    体液的离子环境会影响维持生物体内稳态的神经功能,并确保正常的感知能力和反射活动。神经反射活动,如肢体运动,与钾离子(K+)密切相关。在这项研究中,我们开发了基于离子浓度可调凝胶的人工突触设备,用于模拟体液中不同K浓度下的各种突触可塑性。除了执行基本的突触功能,提出了使用离子浓度可调凝胶实现的短期和长期可塑性在信息处理和联想学习中的潜在应用。人造突触装置可用于构建控制人造肌肉反射活动的人造神经通路,并可用于图像模式识别。所有测试都显示与离子稳态有很强的关系。这些设备可以应用于神经形态机器人和人机界面。
    The ionic environment of body fluids influences nervous functions for maintaining homeostasis in organisms and ensures normal perceptual abilities and reflex activities. Neural reflex activities, such as limb movements, are closely associated with potassium ions (K+). In this study, we developed artificial synaptic devices based on ion concentration-adjustable gels for emulating various synaptic plasticities under different K+ concentrations in body fluids. In addition to performing essential synaptic functions, potential applications in information processing and associative learning using short- and long-term plasticity realized using ion concentration-adjustable gels are presented. Artificial synaptic devices can be used for constructing an artificial neural pathway that controls artificial muscle reflex activities and can be used for image pattern recognition. All tests show a strong relationship with ion homeostasis. These devices could be applied to neuromorphic robots and human-machine interfaces.
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  • 文章类型: Journal Article
    在这项研究中,加工番茄(SolanumlycopersicumL.)\'Ligeer87-5\'在100mMNaCl下进行水培培养,以模拟盐胁迫。为了研究对离子稳态的影响,渗透调节,和番茄幼苗的氧化还原状态,通过叶面施用0.5mMAsA(NA处理)建立了不同内源水平的抗坏血酸(AsA),0.25mM石蒜碱(LYC,AsA合成抑制剂;NL处理),以及LYC和AsA的组合(NLA处理)。结果表明,外源AsA显著提高了NaCl胁迫和NL处理下番茄幼苗叶片中参与AsA合成的关键酶(L-半乳糖-1,4-内酯脱氢酶(GalLDH)和L-半乳糖脱氢酶(GalDH))的活性和基因表达。从而增加细胞AsA含量以维持其还原状态。此外,外源AsA通过SOS途径调节多种离子转运蛋白,增加钾的选择性吸收,Ca2+,和Mg2+在天线部分,重建细胞中的离子稳态,从而缓解盐胁迫引起的离子失衡。外源AsA也增加了脯氨酸脱氢酶(ProDH)活性和基因表达,同时抑制Δ1-吡咯啉-5-羧酸合成酶(P5CS)和鸟氨酸-δ-氨基转移酶(OAT)的活性和转录水平,从而减少叶片中过量的脯氨酸含量并减轻渗透胁迫。LYC加剧了盐胁迫引起的离子失衡和渗透胁迫,应用AsA可以显著逆转。因此,外源AsA施用增加了内源AsA水平,重建离子稳态,保持渗透平衡,有效缓解了盐胁迫对番茄幼苗生长的抑制作用,增强了他们的耐盐性。
    In this study, processing tomato (Solanum lycopersicum L.) \'Ligeer 87-5\' was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion homeostasis, osmotic regulation, and redox status in tomato seedlings, different endogenous levels of ascorbic acid (AsA) were established through the foliar application of 0.5 mM AsA (NA treatment), 0.25 mM lycorine (LYC, an inhibitor of AsA synthesis; NL treatment), and a combination of LYC and AsA (NLA treatment). The results demonstrated that exogenous AsA significantly increased the activities and gene expressions of key enzymes (L-galactono-1,4-lactone dehydrogenase (GalLDH) and L-galactose dehydrogenase (GalDH)) involved in AsA synthesis in tomato seedling leaves under NaCl stress and NL treatment, thereby increasing cellular AsA content to maintain its redox status in a reduced state. Additionally, exogenous AsA regulated multiple ion transporters via the SOS pathway and increased the selective absorption of K+, Ca2+, and Mg2+ in the aerial parts, reconstructing ion homeostasis in cells, thereby alleviating ion imbalance caused by salt stress. Exogenous AsA also increased proline dehydrogenase (ProDH) activity and gene expression, while inhibiting the activity and transcription levels of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine-δ-aminotransferase (OAT), thereby reducing excessive proline content in the leaves and alleviating osmotic stress. LYC exacerbated ion imbalance and osmotic stress caused by salt stress, which could be significantly reversed by AsA application. Therefore, exogenous AsA application increased endogenous AsA levels, reestablished ion homeostasis, maintained osmotic balance, effectively alleviated the inhibitory effect of salt stress on tomato seedling growth, and enhanced their salt tolerance.
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  • 文章类型: Journal Article
    结合生态生理技术和蛋白质组学分析的专性盐生植物的研究对于理解盐分耐性机制至关重要,但有限。因此,我们检查了增长,水关系,离子稳态,光合作用,在半水培培养下,专性盐生植物碱蓬对盐度增加的氧化应激缓解和蛋白质组学反应。大多数生物量参数在中等盐度(300mmolL-1的NaCl)下增加,而高盐度(900mmolL-1的NaCl)导致生物量参数有所下降。在中等盐度下,植物表现出有效的渗透调节,并伴随着Na在根和叶中的积累。Na+的积累并不伴随营养缺乏,用300mmolL-1的NaCl处理对植物的光合机制和氧化损伤。在高盐度下,植物显示树液渗透势进一步下降,Na积累增加,这与相对含水量的下降并不一致,Fv/Fm,和氧化损伤标志物(H2O2和MDA)。在最佳盐度处理中有22、54和7种蛋白质,在高盐度处理中有29、46和8种蛋白质被上调,下调或没有变化,分别,与对照植物相比。这些数据表明,在高盐度条件下,fruitcosa中的生物量减少可能主要是由于增加的能量成本而不是离子毒性。
    Studies on obligate halophytes combining eco-physiological techniques and proteomic analysis are crucial for understanding salinity tolerance mechanisms but are limited. We thus examined growth, water relations, ion homeostasis, photosynthesis, oxidative stress mitigation and proteomic responses of an obligate halophyte Suaeda fruticosa to increasing salinity under semi-hydroponic culture. Most biomass parameters increased under moderate (300 mmol L-1 of NaCl) salinity, while high (900 mmol L-1 of NaCl) salinity caused some reduction in biomass parameters. Under moderate salinity, plants showed effective osmotic adjustment with concomitant accumulation of Na+ in both roots and leaves. Accumulation of Na+ did not accompany nutrient deficiency, damage to photosynthetic machinery and oxidative damage in plants treated with 300 mmol L-1 of NaCl. Under high salinity, plants showed further decline in sap osmotic potential with higher Na+ accumulation that did not coincide with a decline in relative water content, Fv/Fm, and oxidative damage markers (H2O2 and MDA). There were 22, 54 and 7 proteins in optimal salinity and 29, 46 and 8 proteins in high salinity treatment that were up-regulated, down-regulated or exhibited no change, respectively, as compared to control plants. These data indicate that biomass reduction in S. fruticosa at high salinity might result primarily from increased energetic cost rather than ionic toxicity.
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  • 文章类型: Journal Article
    背景:我们以前报道,转移通常以激活组织重塑/血管形成的基因表达的核心程序为特征,改变离子稳态,诱导氧化代谢,并沉默细胞外基质相互作用。该核心程序将转移与它们的起源原发性肿瘤以及它们的目的地宿主组织区分开来。因此,所涉及的基因产物是抗转移药物治疗的潜在靶点.
    方法:因为细胞外基质相互作用的沉默在没有主动生存机制的情况下容易导致anoiks,我们测试了其他三种成分的抑制剂。
    结果:个别地,低特异性VEGFR阻断剂帕唑帕尼(体内联合marimastat),抗氧化剂二甲基亚砜(或替代品阿托瓦醌,经批准用于内部管理),离子调节剂布美他尼和四硫钼酸盐抑制乳腺癌和胰腺癌细胞系的软琼脂集落形成。个体候选药剂具有在人类中使用的记录(当单独施用时具有有限的功效)并且可用于再利用。在组合中,这些药物的作用是累加的或协同的。在两种小鼠癌症模型中(利用4T1细胞或B16-F10细胞),这些药物的联合治疗,立即应用(以防止转移形成)或延迟后(以抑制已建立的转移),大大减少了播散性病灶的发生。
    结论:组织重塑抑制剂的组合,氧化代谢的抑制剂,和离子稳态调节剂对于治疗多种癌症的转移具有很强的前景。
    BACKGROUND: We previously reported that metastases are generally characterized by a core program of gene expression that activates tissue remodeling/vascularization, alters ion homeostasis, induces the oxidative metabolism, and silences extracellular matrix interactions. This core program distinguishes metastases from their originating primary tumors as well as from their destination host tissues. Therefore, the gene products involved are potential targets for anti-metastasis drug treatment.
    METHODS: Because the silencing of extracellular matrix interactions predisposes to anoiks in the absence of active survival mechanisms, we tested inhibitors against the other three components.
    RESULTS: Individually, the low-specificity VEGFR blocker pazopanib (in vivo combined with marimastat), the antioxidant dimethyl sulfoxide (or the substitute atovaquone, which is approved for internal administration), and the ionic modulators bumetanide and tetrathiomolybdate inhibited soft agar colony formation by breast and pancreatic cancer cell lines. The individual candidate agents have a record of use in humans (with limited efficacy when administered individually) and are available for repurposing. In combination, the effects of these drugs were additive or synergistic. In two mouse models of cancer (utilizing 4T1 cells or B16-F10 cells), the combination treatment with these medications, applied immediately (to prevent metastasis formation) or after a delay (to suppress established metastases), dramatically reduced the occurrence of disseminated foci.
    CONCLUSIONS: The combination of tissue remodeling inhibitors, suppressors of the oxidative metabolism, and ion homeostasis modulators has very strong promise for the treatment of metastases by multiple cancers.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    背景:在植物中,GABA在调节盐度胁迫耐受性中起关键作用。然而,大豆幼苗(GlycinemaxL.)在盐胁迫条件下对外源γ-氨基丁酸(GABA)的反应尚未完全阐明。
    结果:本研究调查了外源GABA(2mM)对植物生物量的影响以及大豆植物受到盐水胁迫条件(0、40和80mM的NaCl和Na2SO4摩尔比为1:1)影响的生理机制。我们注意到盐度胁迫的增加对大豆幼苗的生长和代谢产生了负面影响,与控制相比。根-茎-叶生物量(27-和33%,20%和58%,在40-和80mM压力下,分别为25-和59%,分别])和叶绿素a和叶绿素b的浓度显着下降。此外,用40mM胁迫处理后,类胡萝卜素含量显着增加(35%)。结果表明,过氧化氢(H2O2)的浓度显着增加,丙二醛(MDA),脱氢抗坏血酸(DHA)氧化谷胱甘肽(GSSG),Na+,和Cl-在40-和80mM应力水平下,分别。然而,矿物质营养素的浓度,可溶性蛋白质,在两个盐度胁迫水平下,可溶性糖均显着降低。相比之下,与对照组相比,脯氨酸和甘氨酸甜菜碱浓度增加。此外,抗坏血酸过氧化物酶的酶活性,单脱氢抗坏血酸还原酶,谷胱甘肽还原酶,谷胱甘肽过氧化物酶显著下降,而那些超氧化物歧化酶,过氧化氢酶,过氧化物酶,脱氢抗坏血酸还原酶在盐水胁迫后增加,表明抗坏血酸-谷胱甘肽循环(AsA-GSH)的总体敏感性。然而,外源GABA降低Na+,Cl-,H2O2和MDA浓度,但光合色素增强,矿物质营养素(K+,K+/Na+比值,Zn2+,Fe2+,Mg2+,和Ca2+);渗透压(脯氨酸,甘氨酸甜菜碱,可溶性糖,和可溶性蛋白质);酶促抗氧化活性;和AsA-GSH库,从而减少与盐度相关的胁迫损害,并改善生长和生物量。外源施用GABA对大豆植株的积极影响可归因于其改善其生理胁迫应答机制和减少有害物质的能力。
    结论:将GABA应用于大豆植物可能是减轻盐分胁迫的有效策略。在未来,分子研究可能有助于更好地理解GABA调节大豆耐盐性的机制。
    BACKGROUND: In plants, GABA plays a critical role in regulating salinity stress tolerance. However, the response of soybean seedlings (Glycine max L.) to exogenous gamma-aminobutyric acid (GABA) under saline stress conditions has not been fully elucidated.
    RESULTS: This study investigated the effects of exogenous GABA (2 mM) on plant biomass and the physiological mechanism through which soybean plants are affected by saline stress conditions (0, 40, and 80 mM of NaCl and Na2SO4 at a 1:1 molar ratio). We noticed that increased salinity stress negatively impacted the growth and metabolism of soybean seedlings, compared to control. The root-stem-leaf biomass (27- and 33%, 20- and 58%, and 25- and 59% under 40- and 80 mM stress, respectively]) and the concentration of chlorophyll a and chlorophyll b significantly decreased. Moreover, the carotenoid content increased significantly (by 35%) following treatment with 40 mM stress. The results exhibited significant increase in the concentration of hydrogen peroxide (H2O2), malondialdehyde (MDA), dehydroascorbic acid (DHA) oxidized glutathione (GSSG), Na+, and Cl- under 40- and 80 mM stress levels, respectively. However, the concentration of mineral nutrients, soluble proteins, and soluble sugars reduced significantly under both salinity stress levels. In contrast, the proline and glycine betaine concentrations increased compared with those in the control group. Moreover, the enzymatic activities of ascorbate peroxidase, monodehydroascorbate reductase, glutathione reductase, and glutathione peroxidase decreased significantly, while those of superoxide dismutase, catalase, peroxidase, and dehydroascorbate reductase increased following saline stress, indicating the overall sensitivity of the ascorbate-glutathione cycle (AsA-GSH). However, exogenous GABA decreased Na+, Cl-, H2O2, and MDA concentration but enhanced photosynthetic pigments, mineral nutrients (K+, K+/Na+ ratio, Zn2+, Fe2+, Mg2+, and Ca2+); osmolytes (proline, glycine betaine, soluble sugar, and soluble protein); enzymatic antioxidant activities; and AsA-GSH pools, thus reducing salinity-associated stress damage and resulting in improved growth and biomass. The positive impact of exogenously applied GABA on soybean plants could be attributed to its ability to improve their physiological stress response mechanisms and reduce harmful substances.
    CONCLUSIONS: Applying GABA to soybean plants could be an effective strategy for mitigating salinity stress. In the future, molecular studies may contribute to a better understanding of the mechanisms by which GABA regulates salt tolerance in soybeans.
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  • 文章类型: Journal Article
    氯化物是通过调节其稳态和流变过程而参与细胞生理学的关键阴离子。细胞Cl-浓度的变化导致细胞功能的差异调节,如转录和翻译,翻译后修改,细胞周期和增殖,细胞体积,和pH值。在细胞内区室,Cl-调节溶酶体的功能,线粒体,内体,吞噬体,核,和内质网。在细胞外液(ECF)中,Cl-存在于血液/血浆中,和间质液室。ECF中Cl-水平的降低可导致细胞体积收缩。Cl-是关键的生理阴离子,是主要阳离子如Na+运动的主要补偿离子,K+,Ca2+。在过去的25年里,我们增加了对Cl-介导的细胞信号传导的理解,这有助于理解在Cl-水平改变的病理中观察到的分子和代谢变化.这里,我们回顾了不同器官和细胞区室中Cl-的浓度,负责其运输的离子通道,以及有关其生理作用的最新信息。
    Chloride is a key anion involved in cellular physiology by regulating its homeostasis and rheostatic processes. Changes in cellular Cl- concentration result in differential regulation of cellular functions such as transcription and translation, post-translation modifications, cell cycle and proliferation, cell volume, and pH levels. In intracellular compartments, Cl- modulates the function of lysosomes, mitochondria, endosomes, phagosomes, the nucleus, and the endoplasmic reticulum. In extracellular fluid (ECF), Cl- is present in blood/plasma and interstitial fluid compartments. A reduction in Cl- levels in ECF can result in cell volume contraction. Cl- is the key physiological anion and is a principal compensatory ion for the movement of the major cations such as Na+, K+, and Ca2+. Over the past 25 years, we have increased our understanding of cellular signaling mediated by Cl-, which has helped in understanding the molecular and metabolic changes observed in pathologies with altered Cl- levels. Here, we review the concentration of Cl- in various organs and cellular compartments, ion channels responsible for its transportation, and recent information on its physiological roles.
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  • 文章类型: Journal Article
    边缘土地,比如盐渍土,有潜力作为替代资源,用于种植可再生能源和化学品生产中使用的专用生物质作物。边缘土地的优化利用不仅可以缓解耕地与主要粮食作物的竞争,而且还有助于生物能源产品和土壤改良。Miscanthussincarflorus和M.lutarioriparius是主要的多年生植物,适合在盐渍土壤中进行可持续的生物能源生产。然而,他们对盐胁迫的反应在很大程度上仍未被探索。在这项研究中,我们利用318个基因型的糖M.lutarioriparius来评估他们在150mMNaCl下的耐盐性水平,使用14个性状,随后建立了一个迷你核心耐盐精英收藏。我们的结果表明,在评估的基因型中,耐盐性存在很大差异。耐盐基因型表现出显著较低的Na+含量,K+含量与Na+含量呈正相关。有趣的是,芽中Na水平较高的一些基因型显示出改善的芽生长特性。这一观察表明,糖草M.lutarioriparius通过调节离子稳态来适应盐胁迫,主要是通过增强钾的摄取,射击Na+排除,和芽液泡中的Na+固存。全面评价耐盐性,我们根据14个性状的隶属函数值建立了评估值(D值)。我们确定了三个高度耐盐,50耐盐,127中度耐盐,117盐敏感,利用D值在苗期和21个高度盐敏感基因型。建立了苗期花草和花草耐盐性的数学评价模型。值得注意的是,使用CoreHunter算法开发的包含64种基因型的微型核心集合有效地代表了整个集合的整体变异性.这个微型核心集合是一个有价值的基因库,可供将来深入研究芒草的耐盐机制。
    Marginal lands, such as those with saline soils, have potential as alternative resources for cultivating dedicated biomass crops used in the production of renewable energy and chemicals. Optimum utilization of marginal lands can not only alleviate the competition for arable land use with primary food crops, but also contribute to bioenergy products and soil improvement. Miscanthus sacchariflorus and M. lutarioriparius are prominent perennial plants suitable for sustainable bioenergy production in saline soils. However, their responses to salt stress remain largely unexplored. In this study, we utilized 318 genotypes of M. sacchariflorus and M. lutarioriparius to assess their salt tolerance levels under 150 mM NaCl using 14 traits, and subsequently established a mini-core elite collection for salt tolerance. Our results revealed substantial variation in salt tolerance among the evaluated genotypes. Salt-tolerant genotypes exhibited significantly lower Na+ content, and K+ content was positively correlated with Na+ content. Interestingly, a few genotypes with higher Na+ levels in shoots showed improved shoot growth characteristics. This observation suggests that M. sacchariflorus and M. lutarioriparius adapt to salt stress by regulating ion homeostasis, primarily through enhanced K+ uptake, shoot Na+ exclusion, and Na+ sequestration in shoot vacuoles. To evaluate salt tolerance comprehensively, we developed an assessment value (D value) based on the membership function values of the 14 traits. We identified three highly salt-tolerant, 50 salt-tolerant, 127 moderately salt-tolerant, 117 salt-sensitive, and 21 highly salt-sensitive genotypes at the seedling stage by employing the D value. A mathematical evaluation model for salt tolerance was established for M. sacchariflorus and M. lutarioriparius at the seedling stage. Notably, the mini-core collection containing 64 genotypes developed using the Core Hunter algorithm effectively represented the overall variability of the entire collection. This mini-core collection serves as a valuable gene pool for future in-depth investigations of salt tolerance mechanisms in Miscanthus.
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  • 文章类型: Journal Article
    需要具有新作用方式的新药来保护疟疾治疗。近年来,已经测试了数百万种化合物抑制无性血液阶段恶性疟原虫寄生虫生长的能力,从而鉴定出数千种具有抗疟原虫活性的化合物。确定抗疟药化合物的作用机制为其进一步发展提供了依据。但仍然具有挑战性。被鉴定为杀死无性血液阶段寄生虫的化合物的比例相对较高,显示出靶向寄生虫的质膜Na+挤出的证据,H+进口泵,PfATP4。PfATP4抑制剂引起寄生虫内部[Na+]和pH的特征性变化。这里,我们设计了一种“pH指纹”测定法,可以可靠地识别PfATP4抑制剂,同时允许检测(和区分)乳酸的抑制剂:H转运蛋白PfFNT,这是一个有效的抗疟疾药物靶标,和V型H+ATP酶,建议将其作为临床候选ZY19489的可能靶标。在我们的pH指纹分析和随后的二次分析中,ZY19489没有显示V型H+ATP酶抑制pH调节的证据,这表明它在寄生虫中具有不同的作用方式。pH指纹分析还具有鉴定质子团的潜力,酸负载Cl-转运蛋白的抑制剂(分子身份仍然难以捉摸),以及通过抑制葡萄糖转运蛋白PfHT或糖酵解而起作用的化合物。因此,pH指纹测定提供了有效的起点,以匹配一定比例的抗疟原虫化合物及其作用机制。
    New drugs with novel modes of action are needed to safeguard malaria treatment. In recent years, millions of compounds have been tested for their ability to inhibit the growth of asexual blood-stage Plasmodium falciparum parasites, resulting in the identification of thousands of compounds with antiplasmodial activity. Determining the mechanisms of action of antiplasmodial compounds informs their further development, but remains challenging. A relatively high proportion of compounds identified as killing asexual blood-stage parasites show evidence of targeting the parasite\'s plasma membrane Na+-extruding, H+-importing pump, PfATP4. Inhibitors of PfATP4 give rise to characteristic changes in the parasite\'s internal [Na+] and pH. Here, we designed a \"pH fingerprint\" assay that robustly identifies PfATP4 inhibitors while simultaneously allowing the detection of (and discrimination between) inhibitors of the lactate:H+ transporter PfFNT, which is a validated antimalarial drug target, and the V-type H+ ATPase, which was suggested as a possible target of the clinical candidate ZY19489. In our pH fingerprint assays and subsequent secondary assays, ZY19489 did not show evidence for the inhibition of pH regulation by the V-type H+ ATPase, suggesting that it has a different mode of action in the parasite. The pH fingerprint assay also has the potential to identify protonophores, inhibitors of the acid-loading Cl- transporter(s) (for which the molecular identity(ies) remain elusive), and compounds that act through inhibition of either the glucose transporter PfHT or glycolysis. The pH fingerprint assay therefore provides an efficient starting point to match a proportion of antiplasmodial compounds with their mechanisms of action.
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