Search Results (57)

This article presents a conceptual perspective proposing that hypoxia acts as a unifying regulator of plasma membrane phosphohydrolases. We propose that oxygen sensing at the cell surface integrates adenosine and phosphate metabolism to sustain tumour adaptation. Within the oxygen- and nutrient-deprived tumour microenvironment, inorganic phosphate (Pi) and adenosine function as metabolic substrates and signalling mediators that promote cell proliferation, survival, and immune evasion. Stabilisation of hypoxia-inducible factor-1α (HIF-1α) enhances the expression and catalytic activity of specific phosphohydrolases, notably the ectonucleotidases CD39 (NTPDase1) and CD73 (ecto-5′-nucleotidase), which drive adenosine accumulation and immunosuppression. Conversely, the activity of transmembrane prostatic acid phosphatase (TM-PAP), responsible for hydrolysing phosphate esters such as p-nitrophenylphosphate (pNPP) and AMP, is inhibited under hypoxia through oxidative and kinase-dependent mechanisms. Collectively, these mechanisms characterise the plasma membrane as a dynamic metabolic interface, where oxygen sensing coordinates adenosine and phosphate turnover, thereby promoting tumour adaptation across hypoxic environments. We propose that hypoxia orchestrates a dual regulatory loop connecting adenosine accumulation and phosphate turnover at the tumour cell surface, providing a conceptual basis for future mechanistic studies. Full article

Background: The Arabidopsis FCS-LIKE ZINC FINGER (FLZ) family proteins play crucial roles in responses to various biotic and abiotic stresses, but the functions of many family members remain uncharacterized. Methods: In this study, we investigated the function of FLZ12, a member of the FLZ family, using a reverse genetic approach. Results: We found that overexpression of FLZ12 impaired root hair development, as evidenced by marked reductions in both root hair length and number under normal growth conditions. However, deprivation of phosphate could partially restore root hair formation, although it still impeded root hair elongation. Notably, FLZ12-overexpressing lines exhibited greatly enhanced tolerance to iron deficiency, with seedlings exhibiting more vigorous and robust growth compared to wild-type plants. In contrast, knockout of FLZ12 resulted in slight impact on seedling development. Further analysis revealed that FLZ12 accumulation was increased in vascular tissues of plants subjected to iron starvation, and the protein was predominantly localized within the nucleus. Conclusions: Integrating these findings with existing evidence, we propose that FLZ12 functions as a translational regulator through interacting with other proteins, playing dual roles in root hair development and iron-deficiency responses in Arabidopsis. These findings provide new insights into the FLZ-domain-containing proteins and offer molecular strategies to enhance iron uptake efficiency in crops, highlighting FLZ12 as a promising candidate for future breeding efforts. Full article

Viruses can manipulate the host metabolism to achieve optimal replication conditions, and central carbon metabolism (CCM) pathways are often crucial in determining viral infections. Feline calicivirus (FCV), a diminutive RNA viral agent, induces upper respiratory tract infections in feline hosts, with highly pathogenic strains capable of precipitating systemic infections and subsequent host cell necrosis, thereby presenting a formidable challenge to feline survival and protection. However, the relationship between FCV and host cell central carbon metabolism (CCM) remains unclear, and the precise pathogenic mechanisms of FCV are yet to be elucidated. Upon FCV infection of Crandell-Rees Feline Kidney (CRFK) cells, an enhanced cellular uptake of glucose and glutamine was observed. Metabolomics analyses disclosed pronounced alterations in the central carbon metabolism of the infected cells. FCV infection was found to augment glycolytic activity while sustaining the tricarboxylic acid (TCA) cycle flux, with cellular ATP levels remaining invariant. Concurrently, both glutamine metabolism and the flux of the pentose phosphate pathway (PPP) were noted to be intensified. The application of various inhibitory agents targeting glycolysis, glutamine metabolism, and the PPP resulted in a significant suppression of FCV proliferation. Experiments involving glucose and glutamine deprivation demonstrated that the absence of either nutrient markedly curtailed FCV replication. Collectively, these findings suggest a critical interplay between central carbon metabolism and FCV proliferation. FCV infection stimulates CRFK cells to augment glucose and glutamine uptake, thereby supplying the necessary metabolic substrates and energy for viral replication. During the infection, glutamine emerges as the primary energy substrate, ensuring ATP production and energy homeostasis, while glucose is predominantly channeled into the pentose phosphate pathway to facilitate nucleotide synthesis. Full article

Ticks are hematophagous ectoparasites that transmit pathogens and inflict significant economic losses on the cattle industry. Remarkably, they can survive extended periods of starvation in the absence of a host. The primary objective of this study was to investigate the metabolic adaptations that enable the tick Rhipicephalus microplus to endure starvation using the BME26 cell line as a model system. To simulate nutrient deprivation, cells were subjected to starvation conditions by replacing the L-15 culture medium with phosphate-buffered saline (PBS). Our findings show that these tick cells can endure experimental starvation for up to 48 h. The assessment of glycogen levels in starved cells shows a significant decrease, at both the 24 h and 48 h marks. Additionally, upregulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression, along with downregulation of hexokinase (HK) and pyruvate kinase (PK) gene expression, indicated that BME26 cells would prioritize the gluconeogenic pathway over the glycolytic pathway under starvation conditions. Moreover, the transcriptional levels of autophagy-related genes (ATG) were upregulated in response to starvation. Taken together, our findings suggest a potential role for autophagy in supplying substrates for the gluconeogenic pathway in nutrient-deprived tick cells. This work contributes to the understanding of metabolic regulation in R. microplus ticks and offers valuable insights for tick control strategies. Full article

Plants known as obligate aerobes developed different mechanisms to overcome the damage incurred under oxygen limitation. One of the survival strategies to have commonly appeared in hydrophytic plants is the escape strategy, which accelerates plant axial organs’ growth in order to escape hypoxic conditions as soon as possible. The present study aimed to distinguish the alterations in coleoptile elongation, viability and metabolic profiles in coleoptiles of slow- and fast-growing rice varieties. All the parameters were tested at 3, 5 and 7 days after sowing, to highlight changes during seedling development in normal and submerged conditions. The obtained results indicated that coleoptile elongation correlated with higher resistance to oxygen deprivation. GS-MS-based metabolic profiling indicated that coleoptiles of the fast-growing cultivar accumulated higher amounts of sugar phosphates, disaccharides, fatty acid derivatives and sterols, which are important for maintaining growth, membrane stability and viability. The slow-growing variety was characterized by a greater abundance of carboxylates, including lactate and phosphoric acid, indicating an energy crisis and cytosol acidification, leading to cell damage and low tolerance. Therefore, a metabolomics approach could be used for phenotyping (chemotyping) in the large-scale screening of newly developed varieties with higher tolerance to oxygen deprivation. Full article

Phosphorus deficiency critically constrains crop growth. Soil microbial diversity, which is crucial for maintaining terrestrial ecosystem integrity, plays a key role in promoting soil P cycling. Therefore, it is imperative to understand the survival strategies of microorganisms under P-limited conditions and explore their roles in community regulation. We initiated a comprehensive, long-term, in situ wheat field experiment to measure soil physicochemical properties, focusing on the different forms of soil inorganic P. Subsequently, 16S rRNA and ITS marker sequencing was employed to study changes in soil microbial abundance and community structure and predict functional alterations. The results showed that soil water and P deficiencies significantly affected wheat growth and development, soil physicochemical properties, and microbial diversity and function. Prolonged P deficiency lowered soil pH, significantly increasing phosphatase content (58%) under W1 (normal irrigation) conditions. Divalent calcium phosphate decreased significantly under W0 (lack of irrigation) and W1 conditions, and the most stable ten-valent calcium phosphate began to transform under W0 conditions. Soil microbial diversity increased (e.g., Proteobacteria and Vicinamibacterales) and enhanced the transport capacity of bacteria. P deficiency affected the coexistence networks between bacteria and fungi, and SEM (structural equation modeling) analysis revealed a stronger correlation in bacteria (r² = 0.234) than in fungi (r² = 0.172). In soils deprived of P for 7 years, the soil P content and forms were coupled with microbial changes. Microorganisms exhibited community and functional changes in response to low-phosphorus soil, concurrently influencing soil P status. This study enhances our understanding of rhizospheric processes in soil P cycling under microbial feedback, particularly the impact of microbial interactions on changes in soil P forms under P-limited conditions. Full article

Rasagiline (Azilect^®) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symptomatic benefits in Parkinson’s disease (PD) treatment and has been found to exert preclinical neuroprotective effects. Here, we investigated the neuroprotective signaling pathways of acute rasagiline treatment for 22 h in PC12 neuronal cultures exposed to oxygen–glucose deprivation (OGD) for 4 h, followed by 18 h of reoxygenation (R), causing 40% aponecrotic cell death. In this study, 3–10 µM rasagiline induced dose-dependent neuroprotection of 20–80%, reduced the production of the neurotoxic reactive oxygen species by 15%, and reduced the nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by 75–90%. In addition, 10 µM rasagiline increased protein kinase B (Akt) phosphorylation by 50% and decreased the protein expression of the ischemia-induced α-synuclein protein by 50% in correlation with the neuroprotective effect. Treatment with 1–5 µM rasagiline induced nuclear shuttling of transcription factor Nrf2 by 40–90% and increased the mRNA levels of the antioxidant enzymes heme oxygenase-1, (NAD (P) H- quinone dehydrogenase, and catalase by 1.8–2.0-fold compared to OGD/R insult. These results indicate that rasagiline provides neuroprotection to the ischemic neuronal cultures through the inhibition of α-synuclein and GAPDH-mediated aponecrotic cell death, as well as via mitochondrial protection, by increasing mitochondria-specific antioxidant enzymes through a mechanism involving the Akt/Nrf2 redox-signaling pathway. These findings may be exploited for neuroprotective drug development in PD and stroke therapy. Full article

The cell cycle and the transcriptome dynamics of yeast exposed to extracellular self-DNA during an aerobic batch culture on glucose have been investigated using cytofluorimetric and RNA-seq analyses. In parallel, the same study was conducted on yeast cells growing in the presence of (heterologous) nonself-DNA. The self-DNA treatment determined a reduction in the growth rate and a major elongation of the diauxic lag phase, as well as a significant delay in the achievement of the stationary phase. This was associated with significant changes in the cell cycle dynamics, with slower exit from the G0 phase, followed by an increased level of cell percentage in the S phase, during the cultivation. Comparatively, the exposure to heterologous DNA did not affect the growth curve and the cell cycle dynamics. The transcriptomic analysis showed that self-DNA exposure produced a generalized downregulation of transmembrane transport and an upregulation of genes associated with sulfur compounds and the pentose phosphate pathway. Instead, in the case of the nonself treatment, a clear response to nutrient deprivation was detected. Overall, the presented findings represent further insights into the complex functional mechanisms of self-DNA inhibition. Full article

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations in the hypoxic tumor microenvironment, as well as in transcriptional and signaling networks, which result in changes in global genetic expression. The signaling pathways PI3K/AKT/mTOR and RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, by modulating the transcriptional factors p53, HIF1, and c-Myc. The overexpression of HIF1 and c-Myc, master regulators of cellular metabolism, is a key contributor to the synthesis of bioenergetic molecules that mediate glioma cell transformation, proliferation, survival, migration, and invasion by modifying the transcription levels of key gene groups involved in metabolism. Meanwhile, the tumor-suppressing protein p53, which negatively regulates HIF1 and c-Myc, is often lost in glioblastoma. Alterations in this triad of transcriptional factors induce a metabolic shift in glioma cells that allows them to adapt and survive changes such as mutations, hypoxia, acidosis, the presence of reactive oxygen species, and nutrient deprivation, by modulating the activity and expression of signaling molecules, enzymes, metabolites, transporters, and regulators involved in glycolysis and glutamine metabolism, the pentose phosphate cycle, the tricarboxylic acid cycle, and oxidative phosphorylation, as well as the synthesis and degradation of fatty acids and nucleic acids. This review summarizes our current knowledge on the role of HIF1, c-Myc, and p53 in the genic regulatory network for metabolism in glioma cells, as well as potential therapeutic inhibitors of these factors. Full article

Core chlorophytes possess glycerol-3-phosphate dehydrogenases (GPDs) with an unusual bidomain structure, consisting of a glycerol-3-phosphate phosphatase (GPP) domain fused to canonical GPD domains. These plastid-localized enzymes have been implicated in stress responses, being required for the synthesis of glycerol under high salinity and triacylglycerols under nutrient deprivation. However, their regulation under varying environmental conditions is poorly understood. C. reinhardtii transgenic strains expressing constitutively bidomain GPD2 did not accumulate glycerol or triacylglycerols in the absence of any environmental stress. Although the glycerol contents of both wild type and transgenic strains increased significantly upon exposure to high salinity, cycloheximide, an inhibitor of cytoplasmic protein synthesis, abolished this response in the wild type. In contrast, GPD2 transgenic strains were still capable of glycerol accumulation when cultured in medium containing cycloheximide and NaCl. Thus, the pre-existing GPD2 protein appears to become activated for glycerol synthesis upon salt stress. Interestingly, staurosporine, a non-specific inhibitor of protein kinases, prevented this post-translational GPD2 protein activation. Structural modeling analyses suggested that substantial conformational rearrangements, possibly triggered by high salinity, may characterize an active GPD2 GPP domain. Understanding this mechanism(s) may provide insights into the rapid acclimation responses of microalgae to osmotic/salinity stress. Full article

The limited availability of phosphate, nitrogen and silicon in the growth media affects the growth, cellular processes, and metabolism of diatoms. Silicon deficiency primarily affects diatom morphology, while phosphate deficiency reduces the production of nucleic acids and phospholipids. Differences in pigment and protein composition are mainly due to nitrogen deficiency. In this study, Chaetoceros socialis and Chaetoceros costatus were cultured under phosphate, nitrogen, and silicon deprivation conditions. The diatom biomass was collected during the stationary growth phase and extracted with 70% ethanol under ultrasonication. The chemical profiles of the extracts were analyzed by high-performance liquid chromatography with high-resolution mass spectrometry with electrospray ionisation (UHPLC-ESI-HRMS), while the antioxidant capacity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and oxygen radical absorbance capacity (ORAC) assays. Pigments, fatty acids, sterols, and derivatives were detected in both species. The total phenolic content in the extracts ranged from 46.25 ± 1.08 to 89.38 ± 6.21 mg of gallic acid equivalent (GAE)/L and from 29.58 ± 1.08 to 54.17 ± 1.18 mg GAE/L. for C. costatus and C. socialis, respectively. Antioxidant activity was higher in C. costatus extracts, especially those obtained from nitrogen-deprived media. The results of this study contribute to the existing knowledge and the ongoing efforts to overcome application and commercialization barriers of microalgae for wide-ranging potential in different industries. Full article

Phosphate (Pi) starvation is a critical factor limiting crop growth, development, and productivity. Rice (Oryza sativa) R2R3-MYB transcription factors function in the transcriptional regulation of plant responses to various abiotic stresses and micronutrient deprivation, but little is known about their roles in Pi starvation signaling and Pi homeostasis. Here, we identified the R2R3-MYB transcription factor gene OsMYB58, which shares high sequence similarity with AtMYB58. OsMYB58 expression was induced more strongly by Pi starvation than by other micronutrient deficiencies. Overexpressing OsMYB58 in Arabidopsis thaliana and rice inhibited plant growth and development under Pi-deficient conditions. In addition, the overexpression of OsMYB58 in plants exposed to Pi deficiency strongly affected root development, including seminal root, lateral root, and root hair formation. Overexpressing OsMYB58 strongly decreased the expression of the rice microRNAs OsmiR399a and OsmiR399j. By contrast, overexpressing OsMYB58 strongly increased the expression of rice PHOSPHATE 2 (OsPHO2), whose expression is repressed by miR399 during Pi starvation signaling. OsMYB58 functions as a transcriptional repressor of the expression of its target genes, as determined by a transcriptional activity assay. These results demonstrate that OsMYB58 negatively regulates OsmiR399-dependent Pi starvation signaling by enhancing OsmiR399s expression. Full article

Highly porous hydroxyapatite is sometimes considered toxic and useless as a biomaterial for bone tissue regeneration because of the high adsorption of calcium and phosphate ions from cell culture media. This negatively affects the osteoblast’s growth in such ion-deprived media and suggests “false cytotoxicity” of tested hydroxyapatite. In our recent study, we showed that a small addition of calcium sulfate dihydrate (CSD) may compensate for this adsorption without a negative effect on other properties of hydroxyapatite-based biomaterials. This study was designed to verify whether such CSD-supplemented biomaterials may serve as antibiotic carriers. FTIR, roughness, mechanical strength analysis, drug release, hemocompatibility, cytotoxicity against human osteoblasts, and antibacterial activity were evaluated to characterize tested biomaterials. The results showed that the addition of 1.75% gypsum and gentamicin caused short-term calcium ion compensation in media incubated with the composite. The combination of both additives also increased antibacterial activity against bacteria representative of bone infections without affecting osteoblast proliferation, hemocompatibility, and mechanical parameters. Thus, gypsum and antibiotic supplementation may provide advanced functionality for bone-regeneration materials based on hydroxyapatite of a high surface area and increasingly high Ca²⁺ sorption capacity. Full article

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to persistent P deficiency by coordinating the expression of genes involved in the alleviation of stress. Promoters of phosphate transporter genes are a great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and the Saccharum hybrid. To elucidate the function of the 5′ regulatory region, the 1.1 kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using a β-glucuronidase (GUS) assay. The EaPHT1;2 promoter showed 3- to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5′ deletion analysis with and without 5′ UTRs revealed a small-sized 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low-Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops. Full article

Inorganic phosphate (Pi) is actively taken up by Pi transporters (PTs) from the soil and transported into the plant. Here, we functionally characterized the Brassica napus gene BnaPT37, which belongs to the PHT1 family. BnaPT37 is a plasma membrane-localized protein containing 534 amino acids. Expression of BnaPT37 increased significantly under Pi deficiency in various tissues, especially in fully expanded leaves. Expression of the β-glucuronidase reporter gene driven by the BnaPT37 promoter showed that BnaPT37 is expressed in the root, stem, calyx, and leaf under Pi deficiency. BnaPT37 can complement a yeast mutant strain defective in five Pi transporters and can restore the growth of the Arabidopsis atpt1/2 double mutant under Pi deprivation. Overexpression of BnaPT37 in rapeseed significantly increased Pi translocation from root to shoot. Moreover, the movement of Pi from fully expanded leaves to new leaves and roots was enhanced in the transgenic lines compared to the wild type. However, the overexpression of BnaPT37 inhibited the flowering time, plant height, and Pi accumulation in seeds. In conclusion, BnaPT37 functions as a plasma membrane-localized Pi transporter and might be involved in Pi translocation from root to shoot and Pi distribution from source to sink in B. napus. Full article