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1.
Nature ; 603(7902): 637-642, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35322251

RESUMO

The membrane translocation of hydrophilic substances constitutes a challenge for their application as therapeutic compounds and labelling probes1-4. To remedy this, charged amphiphilic molecules have been classically used as carriers3,5. However, such amphiphilic carriers may cause aggregation and non-specific membrane lysis6,7. Here we show that globular dodecaborate clusters, and prominently B12Br122-, can function as anionic inorganic membrane carriers for a broad range of hydrophilic cargo molecules (with molecular mass of 146-4,500 Da). We show that cationic and neutral peptides, amino acids, neurotransmitters, vitamins, antibiotics and drugs can be carried across liposomal membranes. Mechanistic transport studies reveal that the carrier activity is related to the superchaotropic nature of these cluster anions8-12. We demonstrate that B12Br122- affects cytosolic uptake of different small bioactive molecules, including the antineoplastic monomethyl auristatin F, the proteolysis targeting chimera dBET1 and the phalloidin toxin, which has been successfully delivered in living cells for cytoskeleton labelling. We anticipate the broad and distinct delivery spectrum of our superchaotropic carriers to be the starting point of conceptually distinct cell-biological, neurobiological, physiological and pharmaceutical studies.


Assuntos
Boro , Peptídeos , Ânions/química , Transporte Biológico , Cátions , Portadores de Fármacos/química , Interações Hidrofóbicas e Hidrofílicas , Peptídeos/química , Preparações Farmacêuticas
2.
Chem Rev ; 124(5): 2441-2511, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38382032

RESUMO

Boron-containing compounds (BCC) have emerged as important pharmacophores. To date, five BCC drugs (including boronic acids and boroles) have been approved by the FDA for the treatment of cancer, infections, and atopic dermatitis, while some natural BCC are included in dietary supplements. Boron's Lewis acidity facilitates a mechanism of action via formation of reversible covalent bonds within the active site of target proteins. Boron has also been employed in the development of fluorophores, such as BODIPY for imaging, and in carboranes that are potential neutron capture therapy agents as well as novel agents in diagnostics and therapy. The utility of natural and synthetic BCC has become multifaceted, and the breadth of their applications continues to expand. This review covers the many uses and targets of boron in medicinal chemistry.


Assuntos
Boranos , Terapia por Captura de Nêutron de Boro , Neoplasias , Humanos , Boro/química , Química Farmacêutica , Compostos de Boro/química , Neoplasias/tratamento farmacológico , Ácidos Borônicos , Terapia por Captura de Nêutron de Boro/métodos
3.
Plant J ; 117(1): 302-322, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37794835

RESUMO

Understanding how nutrient stress impacts plant growth is fundamentally important to the development of approaches to improve crop production under nutrient limitation. Here we applied single-cell RNA sequencing to shoot apices of Pisum sativum grown under boron (B) deficiency. We identified up to 15 cell clusters based on the clustering of gene expression profiles and verified cell identity with cell-type-specific marker gene expression. Different cell types responded differently to B deficiency. Specifically, the expression of photosynthetic genes in mesophyll cells (MCs) was down-regulated by B deficiency, consistent with impaired photosynthetic rate. Furthermore, the down-regulation of stomatal development genes in guard cells, including homologs of MUTE and TOO MANY MOUTHS, correlated with a decrease in stomatal density under B deficiency. We also constructed the developmental trajectory of the shoot apical meristem (SAM) cells and a transcription factor interaction network. The developmental progression of SAM to MC was characterized by up-regulation of genes encoding histones and chromatin assembly and remodeling proteins including homologs of FASCIATA1 (FAS1) and SWITCH DEFECTIVE/SUCROSE NON-FERMENTABLE (SWI/SNF) complex. However, B deficiency suppressed their expression, which helps to explain impaired SAM development under B deficiency. These results represent a major advance over bulk-tissue RNA-seq analysis in which cell-type-specific responses are lost and hence important physiological responses to B deficiency are missed. The reported findings reveal strategies by which plants adapt to B deficiency thus offering breeders a set of specific targets for genetic improvement. The reported approach and resources have potential applications well beyond P. sativum species and could be applied to various legumes to improve their adaptability to multiple nutrient or abiotic stresses.


Assuntos
Boro , Pisum sativum , Pisum sativum/genética , Boro/metabolismo , Meristema/genética , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética
4.
Nature ; 575(7782): 336-340, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723273

RESUMO

Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials1. The discovery of simpler, milder and more efficient approaches to organoborons can open additional routes to diverse substances2-5. Here we show a general method for the directed C-H borylation of arenes and heteroarenes without the use of metal catalysts. C7- and C4-borylated indoles are produced by a mild approach that is compatible with a broad range of functional groups. The mechanism, which is established by density functional theory calculations, involves BBr3 acting as both a reagent and a catalyst. The potential utility of this strategy is highlighted by the downstream transformation of the formed boron species into natural products and drug scaffolds.


Assuntos
Compostos de Boro/química , Compostos de Boro/síntese química , Boro/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Teoria da Densidade Funcional , Descoberta de Drogas , Indóis/química , Compostos Organometálicos/química , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/química
5.
J Biol Chem ; 299(1): 102740, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36435196

RESUMO

Boric acid is a vital micronutrient in animals; however, excess amounts are toxic to them. Little is known about whole-body boric acid homeostasis in animals. Seawater (SW) contains 0.4 mM boric acid, and since marine fish drink SW, their urinary system was used here as a model of the boric acid excretion system. We determined that the bladder urine of a euryhaline pufferfish (river pufferfish, Takifugu obscurus) acclimated to fresh water and SW contained 0.020 and 19 mM of boric acid, respectively (a 950-fold difference), indicating the presence of a powerful excretory renal system for boric acid. Slc4a11 is a potential animal homolog of the plant boron transporter BOR1; however, mammalian Slc4a11 mediates H+ (OH-) conductance but does not transport boric acid. We found that renal expression of the pufferfish paralog of Slc4a11, Slc4a11A, was markedly induced after transfer from fresh water to SW, and Slc4a11A was localized to the apical membrane of kidney tubules. When pufferfish Slc4a11A was expressed in Xenopus oocytes, exposure to media containing boric acid and a voltage clamp elicited whole-cell outward currents, a marked increase in pHi, and increased boron content. In addition, the activity of Slc4a11A was independent of extracellular Na+. These results indicate that pufferfish Slc4a11A is an electrogenic boric acid transporter that functions as a B(OH)4- uniporter, B(OH)3-OH- cotransporter, or B(OH)3/H+ exchanger. These observations suggest that Slc4a11A is involved in the kidney tubular secretion of boric acid in SW fish, probably induced by the negative membrane potential and low pH of urine.


Assuntos
Boro , Rim , Proteínas de Membrana Transportadoras , Animais , Boro/metabolismo , Rim/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Água do Mar , Peixes , Takifugu
6.
Plant J ; 113(6): 1310-1329, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36658763

RESUMO

Cross-linking of the cell-wall pectin domain rhamnogalacturonan-II (RG-II) via boron bridges between apiose residues is essential for normal plant growth and development, but little is known about its mechanism or reversibility. We characterized the making and breaking of boron bridges in vivo and in vitro at 'apoplastic' pH. RG-II (13-26 µm) was incubated in living Rosa cell cultures and cell-free media with and without 1.2 mm H3 BO3 and cationic chaperones (Ca2+ , Pb2+ , polyhistidine, or arabinogalactan-protein oligopeptides). The cross-linking status of RG-II was monitored electrophoretically. Dimeric RG-II was stable at pH 2.0-7.0 in vivo and in vitro. In-vitro dimerization required a 'catalytic' cation at all pHs tested (1.75-7.0); thus, merely neutralizing the negative charge of RG-II (at pH 1.75) does not enable boron bridging. Pb2+ (20-2500 µm) was highly effective at pH 1.75-4.0, but not 4.75-7.0. Cationic peptides were effective at approximately 1-30 µm; higher concentrations caused less dimerization, probably because two RG-IIs then rarely bonded to the same peptide molecule. Peptides were ineffective at pH 1.75, their pH optimum being 2.5-4.75. d-Apiose (>40 mm) blocked RG-II dimerization in vitro, but did not cleave existing boron bridges. Rosa cells did not take up d-[U-14 C]apiose; therefore, exogenous apiose would block only apoplastic RG-II dimerization in vivo. In conclusion, apoplastic pH neither broke boron bridges nor prevented their formation. Thus boron-starved cells cannot salvage boron from RG-II, and 'acid growth' is not achieved by pH-dependent monomerization of RG-II. Divalent metals and cationic peptides catalyse RG-II dimerization via co-ordinate and ionic bonding respectively (possible and impossible, respectively, at pH 1.75). Exogenous apiose may be useful to distinguish intra- and extra-protoplasmic dimerization.


Assuntos
Boratos , Boro , Ramnogalacturonanos/análise , Chumbo/análise , Pectinas/química , Cátions , Parede Celular/química
7.
Plant J ; 115(5): 1357-1376, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37235684

RESUMO

The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild-type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII-VENUS and DR5-GFP lines) in B-deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis-related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport-related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN-Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis-related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Boro/metabolismo , Raízes de Plantas/metabolismo
8.
Plant J ; 114(1): 176-192, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36721978

RESUMO

The supply of boron (B) alleviates the toxic effects of aluminum (Al) on root growth; however, the mechanistic basis of this process remains elusive. This study filled this knowledge gap, demonstrating that boron modifies auxin distribution and transport in Al-exposed Arabidopsis roots. In B-deprived roots, treatment with Al induced an increase in auxin content in the root apical meristem zone (MZ) and transition zone (TZ), whereas in the elongation zone (EZ) the auxin content was decreased beyond the level required for adequate growth. These distribution patterns are explained by the fact that basipetal auxin transport from the TZ to the EZ was disrupted by Al-inhibited PIN-FORMED 2 (PIN2) endocytosis. Experiments involving the modulation of protein biosynthesis by cycloheximide (CHX) and transcriptional regulation by cordycepin (COR) demonstrated that the Al-induced increase of PIN2 membrane proteins was dependent upon the inhibition of PIN2 endocytosis, rather than on the transcriptional regulation of the PIN2 gene. Experiments reporting on the profiling of Al3+ and PIN2 proteins revealed that the inhibition of endocytosis of PIN2 proteins was the result of Al-induced limitation of the fluidity of the plasma membrane. The supply of B mediated the turnover of PIN2 endosomes conjugated with indole-3-acetic acid (IAA), and thus restored the Al-induced inhibition of IAA transport through the TZ to the EZ. Overall, the reported results demonstrate that boron supply mediates PIN2 endosome-based auxin transport to alleviate Al toxicity in plant roots.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Alumínio/toxicidade , Alumínio/metabolismo , Boro/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Raízes de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Arabidopsis/metabolismo
9.
Cancer Sci ; 115(8): 2774-2785, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38860412

RESUMO

Metastatic spinal tumors are increasingly prevalent due to advancements in cancer treatment, leading to prolonged survival rates. This rising prevalence highlights the need for developing more effective therapeutic approaches to address this malignancy. Boron neutron capture therapy (BNCT) offers a promising solution by delivering targeted doses to tumors while minimizing damage to normal tissue. In this study, we evaluated the efficacy and safety of BNCT as a potential therapeutic option for spine metastases in mouse models induced by A549 human lung adenocarcinoma cells. The animal models were randomly allocated into three groups: untreated (n = 10), neutron irradiation only (n = 9), and BNCT (n = 10). Each mouse was administered 4-borono-L-phenylalanine (250 mg/kg) intravenously, followed by measurement of boron concentrations 2.5 h later. Overall survival, neurological function of the hindlimb, and any adverse events were assessed post irradiation. The tumor-to-normal spinal cord and blood boron concentration ratios were 3.6 and 2.9, respectively, with no significant difference observed between the normal and compressed spinal cord tissues. The BNCT group exhibited significantly prolonged survival rates compared with the other groups (vs. untreated, p = 0.0015; vs. neutron-only, p = 0.0104, log-rank test). Furthermore, the BNCT group demonstrated preserved neurological function relative to the other groups (vs. untreated, p = 0.0004; vs. neutron-only, p = 0.0051, multivariate analysis of variance). No adverse events were observed post irradiation. These findings indicate that BNCT holds promise as a novel treatment modality for metastatic spinal tumors.


Assuntos
Terapia por Captura de Nêutron de Boro , Modelos Animais de Doenças , Neoplasias da Coluna Vertebral , Terapia por Captura de Nêutron de Boro/métodos , Animais , Camundongos , Humanos , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Células A549 , Medula Espinal/efeitos da radiação , Medula Espinal/patologia , Linhagem Celular Tumoral , Boro/uso terapêutico , Feminino
10.
Anal Chem ; 96(14): 5640-5647, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38551637

RESUMO

Detection and discrimination of fluoroquinolones (FQs) are crucial for food safety but remain a formidable challenge due to their minor differences in molecular structures and the serious interferences from food matrices. Herein, we propose an afterglow assay for the detection and discrimination of FQs through modulating their room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF) properties by a host-guest doping strategy. FQs were doped into the boric acid host, forming boronic anhydride structures and hydrogen bonds, which prompted the RTP and TADF performance of FQs by stabilizing their excited states, preventing triplet exciton quenching, and reducing the energy gap between singlet and triplet states. The FQs can be quantitatively detected through monitoring the afterglow intensity of host-guest systems, as low as 0.25 µg/mL. The differences in the afterglow intensity and emission lifetime allowed accurate discrimination of 11 types of FQs through pattern recognition methods. Aided by the delayed signal detection model of afterglow emission, the background signal and the interferences from food matrices were effectively eliminated, which endow the detection and discrimination of mixed FQs in commercial meat samples, without multiple-step separation processes.


Assuntos
Anidridos , Fluoroquinolonas , Bioensaio , Boro , Alimentos
11.
BMC Plant Biol ; 24(1): 9, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163908

RESUMO

BACKGROUND: Essential micronutrient Boron (B) plays crucial roles in plant survival and reproduction but becomes toxic in higher quantities. Although plant cells have different B transport systems, B homeostasis is mainly maintained by two transporter protein families: B exporters (BOR) and nodulin-26-like intrinsic proteins (NIP). Their diversity and differential expression are responsible for varied B tolerance among plant varieties and species. Longan is a highly admired subtropical fruit with a rising market in China and beyond. In the present study, we cultured Shixia (SX) and Yiduo (YD), two differently characterized Longan cultivars, with foliar B spray. We analyzed their leaf physiology, fruit setting, B content, and boron transporter gene expression of various tissue samples. We also traced some of these genes' subcellular localization and overexpression effects. RESULTS: YD and SX foliage share similar microstructures, except the mesophyll cell wall thickness is double in YD. The B spray differently influenced their cellular constituents and growth regulators. Gene expression analysis showed reduced BOR genes expression and NIP genes differential spatiotemporal expression. Using green fluorescent protein, two high-expressing NIPs, NIP1 and NIP19, were found to translocate in the transformed tobacco leaves' cell membrane. NIPs transformation of SX pollen was confirmed using magnetic beads and quantified using a fluorescence microscope and polymerase chain reaction. An increased seed-setting rate was observed when YD was pollinated using these pollens. Between the DlNIP1 and DlNIP19 transformed SX pollen, the former germinated better with increasing B concentrations and, compared to naturally pollinated plants, had a better seed-setting rate in YD♀ × SX♂. CONCLUSION: SX and YD Longan have different cell wall structures and react differently to foliar B spray, indicating distinct B tolerance and management. Two B transporter NIP genes were traced to localize in the plasma membrane. However, under high B concentrations, their differential expression resulted in differences in Jasmonic acid content, leading to differences in germination rate. Pollination of YD using these NIPs transformed SX pollen also showed NIP1 overexpression might overcome the unilateral cross incompatibility between YD♀ × SX♂ and can be used to increase Longan production.


Assuntos
Boro , Proteínas de Membrana Transportadoras , Boro/metabolismo , Transporte Biológico , Proteínas de Membrana Transportadoras/genética , Plantas/metabolismo , Proteínas de Transporte/metabolismo , Homeostase
12.
BMC Plant Biol ; 24(1): 689, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030471

RESUMO

BACKGROUND: Boron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem. RESULTS: We conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery. CONCLUSION: Our results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.


Assuntos
Boro , Nicotiana , Proteoma , Transcriptoma , Boro/deficiência , Boro/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Proteoma/metabolismo , Regulação da Expressão Gênica de Plantas , Plântula/genética , Plântula/metabolismo , Plântula/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica
13.
BMC Plant Biol ; 24(1): 138, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38408911

RESUMO

Micronutrient application has a crucial role in mitigating salinity stress in crop plants. This study was carried out to investigate the effect of zinc (Zn) and boron (B) as foliar applications on fenugreek growth and physiology under salt stress (0 and 120 mM). After 35 days of salt treatments, three levels of zinc (0, 50, and 100 ppm) and two levels of boron (0 and 2 ppm) were applied as a foliar application. Salinity significantly reduced root length (72.7%) and shoot length (33.9%), plant height (36%), leaf area (37%), root fresh weight (48%) and shoot fresh weight (75%), root dry weight (80%) and shoot dry weight (67%), photosynthetic pigments (78%), number of branches (50%), and seeds per pod (56%). Fenugreek's growth and physiology were improved by foliar spray of zinc and boron, which increased the length of the shoot (6%) and root length (2%), fresh root weight (18%), and dry root weight (8%), and chlorophyll a (1%), chlorophyll b (25%), total soluble protein content (3%), shoot calcium (9%) and potassium (5%) contents by significantly decreasing sodium ion (11%) content. Moreover, 100 ppm of Zn and 2 ppm of B enhanced the growth and physiology of fenugreek by reducing the effect of salt stress. Overall, boron and zinc foliar spray is suggested for improvement in fenugreek growth under salinity stress.


Assuntos
Trigonella , Zinco , Boro/metabolismo , Boro/farmacologia , Clorofila A/metabolismo , Estresse Salino , Tensoativos/metabolismo , Tensoativos/farmacologia , Trigonella/metabolismo , Zinco/metabolismo , Zinco/farmacologia
14.
BMC Plant Biol ; 24(1): 550, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872083

RESUMO

BACKGROUND: Boron (B) is a micronutrient, but excessive levels can cause phytotoxicity, impaired growth, and reduced photosynthesis. B toxicity arises from over-fertilization, high soil B levels, or irrigation with B-rich water. Conversely, silicon (Si) is recognized as an element that mitigates stress and alleviates the toxic effects of certain nutrients. In this study, to evaluate the effect of different concentrations of Si on maize under boron stress conditions, a factorial experiment based on a randomized complete block design was conducted with three replications in a hydroponic system. The experiment utilized a nutrient solution for maize var. Merit that contained three different boron (B) concentrations (0.5, 2, and 4 mg L-1) and three Si concentrations (0, 28, and 56 mg L-1). RESULTS: Our findings unveiled that exogenous application of B resulted in a substantial escalation of B concentration in maize leaves. Furthermore, B exposure elicited a significant diminution in fresh and dry plant biomass, chlorophyll index, chlorophyll a (Chl a), chlorophyll b (Chl b), carotenoids, and membrane stability index (MSI). As the B concentration augmented, malondialdehyde (MDA) content and catalase (CAT) enzyme activity exhibited a concomitant increment. Conversely, the supplementation of Si facilitated an amelioration in plant fresh and dry weight, total carbohydrate, and total soluble protein. Moreover, the elevated activity of antioxidant enzymes culminated in a decrement in hydrogen peroxide (H2O2) and MDA content. In addition, the combined influence of Si and B had a statistically significant impact on the leaf chlorophyll index, total chlorophyll (a + b) content, Si and B accumulation levels, as well as the enzymatic activities of guaiacol peroxidase (GPX), ascorbate peroxidase (APX), and H2O2 levels. These unique findings indicated the detrimental impact of B toxicity on various physiological and biochemical attributes of maize, while highlighting the potential of Si supplementation in mitigating the deleterious effects through modulation of antioxidant machinery and biomolecule synthesis. CONCLUSIONS: This study highlights the potential of Si supplementation in alleviating the deleterious effects of B toxicity in maize. Increased Si consumption mitigated chlorophyll degradation under B toxicity, but it also caused a significant reduction in the concentrations of essential micronutrients iron (Fe), copper (Cu), and zinc (Zn). While Si supplementation shows promise in counteracting B toxicity, the observed decrease in Fe, Cu, and Zn concentrations warrants further investigation to optimize this approach and maintain overall plant nutritional status.


Assuntos
Boro , Clorofila , Hidroponia , Silício , Zea mays , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimento , Zea mays/fisiologia , Zea mays/metabolismo , Boro/toxicidade , Boro/metabolismo , Silício/farmacologia , Clorofila/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Malondialdeído/metabolismo , Carotenoides/metabolismo , Antioxidantes/metabolismo , Catalase/metabolismo
15.
Small ; 20(4): e2307029, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37712137

RESUMO

Chemodynamic therapy (CDT) is a highly targeted approach to treat cancer since it converts hydrogen peroxide into harmful hydroxyl radicals (OH·) through Fenton or Fenton-like reactions. However, the systemic toxicity of metal-based CDT agents has limited their clinical applications. Herein, a metal-free CDT agent: 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPT)/ [closo-B12 H12 ]2- (TPT@ B12 H12 ) is reported. Compared to the traditional metal-based CDT agents, TPT@B12 H12 is free of metal avoiding cumulative toxicity during long-term therapy. Density functional theory (DFT) calculation revealed that TPT@B12 H12 decreased the activation barrier more than 3.5 times being a more effective catalyst than the Fe2+ ion (the Fenton reaction), which decreases the barrier about twice. Mechanismly, the theory calculation indicated that both [B12 H12 ]-· and [TPT-H]2+ have the capacity to decompose hydrogen into 1 O2 , OH·, and O2 -· . With electron paramagnetic resonance and fluorescent probes, it is confirmed that TPT@B12 H12 increases the levels of 1 O2 , OH·, and O2 -· . More importantly, TPT@B12 H12 effectively suppress the melanoma growth both in vitro and in vivo through 1 O2 , OH·, and O2 -· generation. This study specifically highlights the great clinical translational potential of TPT@B12 H12 as a CDT reagent.


Assuntos
Melanoma , Neoplasias , Humanos , Melanoma/tratamento farmacológico , Boro , Corantes Fluorescentes , Hidrogênio , Peróxido de Hidrogênio , Metais , Linhagem Celular Tumoral
16.
New Phytol ; 243(5): 1795-1809, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38622812

RESUMO

Boron (B) is crucial for plant growth and development. B deficiency can impair numerous physiological and metabolic processes, particularly in root development and pollen germination, seriously impeding crop growth and yield. However, the molecular mechanism underlying boron signal perception and signal transduction is rather limited. In this study, we discovered that CPK10, a calcium-dependent protein kinase in the CPK family, has the strongest interaction with the boron transporter BOR1. Mutations in CPK10 led to growth and root development defects under B-deficiency conditions, while constitutively active CPK10 enhanced plant tolerance to B deficiency. Furthermore, we found that CPK10 interacted with and phosphorylated BOR1 at the Ser689 residue. Through various biochemical analyses and complementation of B transport in yeast and plants, we revealed that Ser689 of BOR1 is important for its transport activity. In summary, these findings highlight the significance of the CPK10-BOR1 signaling pathway in maintaining B homeostasis in plants and provide targets for the genetic improvement of crop tolerance to B-deficiency stress.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Boro , Raízes de Plantas , Adaptação Fisiológica/genética , Antiporters/metabolismo , Antiporters/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Transporte Biológico , Boro/metabolismo , Boro/deficiência , Regulação da Expressão Gênica de Plantas , Mutação/genética , Fosforilação , Raízes de Plantas/metabolismo , Ligação Proteica , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Transdução de Sinais
17.
New Phytol ; 241(2): 747-763, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37964509

RESUMO

Land plants evolved multiple adaptations to restrict transpiration. However, the underlying molecular mechanisms are not sufficiently understood. We used an ozone-sensitivity forward genetics approach to identify Arabidopsis thaliana mutants impaired in gas exchange regulation. High water loss from detached leaves and impaired decrease of leaf conductance in response to multiple stomata-closing stimuli were identified in a mutant of MURUS1 (MUR1), an enzyme required for GDP-l-fucose biosynthesis. High water loss observed in mur1 was independent from stomatal movements and instead could be linked to metabolic defects. Plants defective in import of GDP-l-Fuc into the Golgi apparatus phenocopied the high water loss of mur1 mutants, linking this phenotype to Golgi-localized fucosylation events. However, impaired fucosylation of xyloglucan, N-linked glycans, and arabinogalactan proteins did not explain the aberrant water loss of mur1 mutants. Partial reversion of mur1 water loss phenotype by borate supplementation and high water loss observed in boron uptake mutants link mur1 gas exchange phenotypes to pleiotropic consequences of l-fucose and boron deficiency, which in turn affect mechanical and morphological properties of stomatal complexes and whole-plant physiology. Our work emphasizes the impact of fucose metabolism and boron uptake on plant-water relations.


Assuntos
Arabidopsis , Fucose , Fucose/metabolismo , Guanosina Difosfato Fucose/metabolismo , Boro/metabolismo , Arabidopsis/metabolismo , Polissacarídeos/metabolismo
18.
J Exp Bot ; 75(8): 2574-2583, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38307018

RESUMO

Transcriptional regulation is a crucial component of plant adaptation to numerous different stresses; however, its role in how plants adapt to low-boron (B) stress remains unclear. In this study, we show that the C2H2-type transcription factor SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) in Arabidopsis is essential for improving plant growth under low-B conditions. STOP1 and the boric acid-channel protein NOD26-LIKE MAJOR INTRINSIC PROTEIN5;1 (NIP5;1) were found to co-localize in root epidermal cells, and STOP1 binds to the 5´-untranslated region of NIP5;1 to activate its expression and enhance B uptake by the roots. Overexpression of STOP1 increased tolerance to low-B stress by up-regulating NIP5;1 transcript levels. Further genetic analyses revealed that STOP1 and NIP5;1 function together in the same pathway to confer low-B tolerance. These results highlight the importance of the STOP1-NIP5;1 module in improving plant growth under low-B conditions.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Transporte Biológico , Boro , Regulação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genética , Fatores de Transcrição/genética
19.
J Biol Inorg Chem ; 29(1): 75-85, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38123706

RESUMO

Metallic titanium (Ti) implant surfaces need improvement for bioproperties and antibacterial behavior. For this purpose, a new boron-doped bioactive apatite-wollastonite (AW) coating was successfully developed on the Ti plate surface. The effects of boron addition on the microstructure, mechanical properties, and bioproperties of the AW coating were investigated. With the addition of boron (B), the AW coating morphology became less porous and compact. In terms of bio properties, the rate of apatite formation increased with the addition of B, and the cell viability rate increased from approximately 66-81%. B addition increased the elastic modulus of the AW coating from about 24-46 GPa and increased its hardness about 2.5 times. In addition, while no antibacterial activity was observed in the AW coating, the addition of boron slightly introduced antibacterial properties. The novel AW/B composite coating obtained is promising for Ti implant surfaces.


Assuntos
Apatitas , Compostos de Cálcio , Cerâmica , Silicatos , Titânio , Apatitas/química , Titânio/farmacologia , Titânio/química , Boro , Antibacterianos/farmacologia , Propriedades de Superfície
20.
Plant Cell ; 33(2): 420-438, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33866370

RESUMO

Plants take up and translocate nutrients through transporters. In Arabidopsis thaliana, the borate exporter BOR1 acts as a key transporter under boron (B) limitation in the soil. Upon sufficient-B supply, BOR1 undergoes ubiquitination and is transported to the vacuole for degradation, to avoid overaccumulation of B. However, the mechanisms underlying B-sensing and ubiquitination of BOR1 are unknown. In this study, we confirmed the lysine-590 residue in the C-terminal cytosolic region of BOR1 as the direct ubiquitination site and showed that BOR1 undergoes K63-linked polyubiquitination. A forward genetic screen identified that amino acid residues located in vicinity of the substrate-binding pocket of BOR1 are essential for the vacuolar sorting. BOR1 variants that lack B-transport activity showed a significant reduction of polyubiquitination and subsequent vacuolar sorting. Coexpression of wild-type (WT) and a transport-defective variant of BOR1 in the same cells showed degradation of the WT but not the variant upon sufficient-B supply. These findings suggest that polyubiquitination of BOR1 relies on its conformational transition during the transport cycle. We propose a model in which BOR1, as a B transceptor, directly senses the B concentration and promotes its own polyubiquitination and vacuolar sorting for quick and precise maintenance of B homeostasis.


Assuntos
Antiporters/metabolismo , Proteínas de Arabidopsis/metabolismo , Boro/farmacologia , Proteólise/efeitos dos fármacos , Ubiquitinação , Sequência de Aminoácidos , Substituição de Aminoácidos , Antiporters/química , Proteínas de Arabidopsis/química , Sítios de Ligação , Testes Genéticos , Proteínas de Fluorescência Verde/metabolismo , Lisina/metabolismo , Modelos Biológicos , Poliubiquitina/metabolismo , Transporte Proteico/efeitos dos fármacos , Prótons , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Especificidade por Substrato , Ubiquitinação/efeitos dos fármacos , Vacúolos/metabolismo
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