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Keywords = inorganic polyphosphate

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15 pages, 4141 KB  
Article
Fabrication and Properties of Chitosan/Calcium Polyphosphate Fibre Composite Biological Scaffold
by Xiaohu Qiang, Zhu Hu, Wang Liu and Dajian Huang
Gels 2025, 11(10), 767; https://doi.org/10.3390/gels11100767 - 24 Sep 2025
Viewed by 51
Abstract
Natural biomaterials are widely used in the construction of cartilage tissue engineering due to their excellent biocompatibility, easy degradation, and ability to degrade products to be absorbed by the human body. However, due to their poor mechanical properties, it is usually necessary to [...] Read more.
Natural biomaterials are widely used in the construction of cartilage tissue engineering due to their excellent biocompatibility, easy degradation, and ability to degrade products to be absorbed by the human body. However, due to their poor mechanical properties, it is usually necessary to composite them with other materials to prepare biological scaffolds that meet the expected requirements. This study used freeze-drying technology to introduce calcium polyphosphate fibres (CPPFs) into a chitosan (CS) matrix to prepare composite scaffolds with better performance. CPPF was used as a filler and inorganic skeleton in the CS/CPPF composite to improve the properties of the CS-based scaffold. With little change in porosity, the compressive strength of the CS/CPPF composite scaffold increased from 0.172 MPa of chitosan to 0.332 MPa with the increase in CPPF addition. The water absorption rate of the composite scaffold decreased from 1297.42% to 935.37%. In vitro degradation experiments revealed that CPPF accelerated the degradation of the scaffold and generated calcium phosphate and nano-hydroxyapatite compounds during the degradation process. According to our cytotoxicity testing, the CS/CPPF composite scaffolds exhibited good biocompatibility and could enhance cell proliferation. This method of incorporating CPPF into CS provides important reference values for the application of CPPF in other natural bone tissue engineering scaffold materials. Full article
(This article belongs to the Special Issue Synthesis and Application of Aerogel (2nd Edition))
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22 pages, 4024 KB  
Article
Inorganic Polyphosphate Modulates Chromosome Transmission Fidelity in the Fission Yeast Schizosaccharomyces pombe
by Sarune Bollé, Elisa Koc, Adolfo Saiardi, Lisa Juhran, Eva Walla, Ursula Fleig and Abel Alcázar-Román
Biomolecules 2025, 15(9), 1331; https://doi.org/10.3390/biom15091331 - 18 Sep 2025
Viewed by 338
Abstract
Chromosome transmission fidelity is vital for organism fitness. Yet, extrinsic and intrinsic changes can affect this process, leading to aneuploidy, the loss/gain of chromosomes, which is a hallmark of cancer. Here, using a haploid fission yeast Schizosaccharomyces pombe strain with a segmental aneuploidy, [...] Read more.
Chromosome transmission fidelity is vital for organism fitness. Yet, extrinsic and intrinsic changes can affect this process, leading to aneuploidy, the loss/gain of chromosomes, which is a hallmark of cancer. Here, using a haploid fission yeast Schizosaccharomyces pombe strain with a segmental aneuploidy, we assayed genome stability under different temperatures and altered gene dosage. We find that S. pombe genome stability is temperature-dependent and is unexpectedly modulated by intracellular levels of inorganic polyphosphate polymers (polyP). The vtc4+ gene, encoding a subunit of the polyP-generating VTC complex, is present twice due to the segmental aneuploidy resulting in a gene-dosage-coupled increase in polyP. Using strains with different amounts of polyP, we find a direct negative correlation between polyP and chromosome segregation fidelity. PolyP modulates the function of the conserved CCAN kinetochore subcomplex, as the abnormal growth phenotype caused by the mutant CCAN protein Fta2-291 was rescued in the absence of polyP, while extra polyP had the opposite effect. Importantly, this appears to occur in part by modulation of the nucleolin Gar2. Gar2 is the functional homolog of the Saccharomyces cerevisiae Nsr1 protein, whose function is modulated by posttranslational polyP-mediated polyphosphorylation. Thus, polyP modulates genome stability, linking cellular metabolism to chromosome transmission fidelity. Full article
(This article belongs to the Special Issue Polyphosphate (PolyP) in Health and Disease)
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25 pages, 3119 KB  
Article
Inorganic Polyphosphate Triggers NLRP3 Inflammasome and Promotes the Epithelial-to-Mesenchymal Transition and Migration of Colorectal Cancer Cells Through TRPM8 Receptor
by Valentina Arrè, Maria Principia Scavo, Rossella Donghia, Francesco Dituri, Camilla Mandorino, Marco Cassotta, Anna Ancona, Francesco Balestra, Leonardo Vincenti, Fabrizio Aquilino, Giuseppe Pettinato, Gianluigi Giannelli and Roberto Negro
Int. J. Mol. Sci. 2025, 26(16), 7743; https://doi.org/10.3390/ijms26167743 - 11 Aug 2025
Viewed by 532
Abstract
Inorganic polyphosphate (iPolyP) is a ubiquitous molecule composed of a variable number of orthophosphate units. Recent studies have highlighted its involvement in colorectal cancer (CRC) cell proliferation. However, further investigations are needed to elucidate its role in CRC cell progression and migration, as [...] Read more.
Inorganic polyphosphate (iPolyP) is a ubiquitous molecule composed of a variable number of orthophosphate units. Recent studies have highlighted its involvement in colorectal cancer (CRC) cell proliferation. However, further investigations are needed to elucidate its role in CRC cell progression and migration, as well as its influence on the tumor microenvironment. This study focuses on the inorganic polyphosphate (iPolyP)/transient receptor potential cation channel subfamily M member 8 (TRPM8) axis and its impact on CRC progression. To investigate these issues, western blotting, fixed and live cells immunofluorescence, 2D and 3D cell culture on CRC-patient derived tissues, ELISA, and wound healing assays were performed. Our results show that inorganic polyphosphate induces the expression of epithelial-to-mesenchymal transition (EMT) markers in CRC cells. Furthermore, the iPolyP/TRPM8 axis indirectly promotes tumor growth through activation of the Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain-containing protein 3 (NLRP3) inflammasome in immune cells, leading to increased levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the tumor microenvironment (TME), thereby advancing CRC. These findings suggest that targeting the iPolyP/TRPM8 pathway may be a promising strategy to inhibit CRC progression and metastasis. Full article
(This article belongs to the Special Issue Colorectal Cancer: Molecular and Cellular Basis)
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29 pages, 1763 KB  
Review
Inorganic Polyphosphate: An Emerging Regulator of Neuronal Bioenergetics and Its Implications in Neuroprotection
by Marcela Montilla, Norma Pavas-Escobar, Iveth Melissa Guatibonza-Arévalo, Alejandro Múnera, Renshen Eduardo Rivera-Melo and Felix A. Ruiz
Biomolecules 2025, 15(8), 1060; https://doi.org/10.3390/biom15081060 - 22 Jul 2025
Viewed by 824
Abstract
Inorganic polyphosphate (polyP) is an evolutionarily conserved polymer that has recently gained relevance in neuronal physiology and pathophysiology. Although its roles, such as mitochondrial bioenergetics, calcium homeostasis, and the oxidative stress response, for example, are increasingly recognized, its specific implications in neurological disorders [...] Read more.
Inorganic polyphosphate (polyP) is an evolutionarily conserved polymer that has recently gained relevance in neuronal physiology and pathophysiology. Although its roles, such as mitochondrial bioenergetics, calcium homeostasis, and the oxidative stress response, for example, are increasingly recognized, its specific implications in neurological disorders remain underexplored. This review focuses on synthesizing the current knowledge of polyP in the context of central nervous system (CNS) diseases, highlighting how its involvement in key mitochondrial processes may influence neuronal survival and function. In particular, we examine recent evidence linking polyP to mechanisms relevant to neurodegeneration, such as the modulation of the mitochondrial permeability transition pore (mPTP), regulation of amyloid fibril formation, and oxidative stress responses. In addition, we analyze the emerging roles of polyP in inflammation and related cell signaling in CNS disorders. By organizing the existing data around the potential pathological and protective roles of polyP in the CNS, this review identifies it as a candidate of interest in the context of neurodegenerative disease mechanisms. We aim to clarify its relevance and stimulate future research on its molecular mechanisms and translational potential. Full article
(This article belongs to the Special Issue Polyphosphate (PolyP) in Health and Disease)
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23 pages, 7168 KB  
Article
Enhancing Soil Phosphorus Availability in Intercropping Systems: Roles of Plant Growth Regulators
by Chunhua Gao, Weilin Kong, Fengtao Zhao, Feiyan Ju, Ping Liu, Zongxin Li, Kaichang Liu and Haijun Zhao
Agronomy 2025, 15(7), 1748; https://doi.org/10.3390/agronomy15071748 - 20 Jul 2025
Viewed by 826
Abstract
Plant growth regulators (PGRs) enhance crop stress resistance but their roles in microbial-mediated phosphorus cycling within intercropping systems are unclear. Thus, We conducted a two-year field study using corn (Zea mays L. cv. Denghai 605) and soybean (Glycine max L. cv. [...] Read more.
Plant growth regulators (PGRs) enhance crop stress resistance but their roles in microbial-mediated phosphorus cycling within intercropping systems are unclear. Thus, We conducted a two-year field study using corn (Zea mays L. cv. Denghai 605) and soybean (Glycine max L. cv. Hedou 22) in fluvisols and luvisols soil according to World Reference Base for Soil Resources (WRB) standard. Under a 4-row corn and 6-row soybean strip intercropping system, three treatments were applied: a water control (CK), and two plant growth regulators—T1 (EC: ethephon [300 mg/L] + cycocel [2 g/L]) and T2 (ED: ethephon [300 mg/L] + 2-Diethyl aminoethyl hexanoate [10 mg/L]). Foliar applications were administered at the V7 stage (seventh leaf) of intercropped corn plants to assess how foliar-applied PGRs (T1/T2) modulated the soil phosphorus availability, microbial communities, and functional genes in maize intercropping systems. PGRs increased the soil organic phosphorus and available phosphorus contents, and alkaline phosphatase activity, but not total phosphorus. PGRs declined the α-diversity in fluvisols soil but increased the α-diversity in luvisols soil. The major taxa changed from Actinobacteria (CK) to Proteobacteria (T1) and Saccharibacteria (T2) in fluvisols soil, and from Actinobacteria/Gemmatimonadetes (CK) to Saccharibacteria (T1) and Acidobacteria (T2) in luvisols soil. Functional gene dynamics indicated soil-specific regulation, where fluvisols soil harbored more phoD (organic phosphorus mineralization) and relA (polyphosphate degradation) genes, whereas phnP gene dominated in luvisols soil. T1 stimulated organic phosphorus mineralization and inorganic phosphorus solubilization in fluvisols soil, upregulating regulation genes, and T2 enhanced polyphosphate synthesis and transport gene expression in luvisols soil. Proteobacteria, Nitrospirae, and Chloroflexi were positively correlated with organic phosphorus mineralization and polyphosphate cycling genes, whereas Bacteroidetes and Verrucomicrobia correlated with available potassium (AP), total phosphorus (TP), and alkaline phosphatase (ALP) activity. Thus, PGRs activated soil phosphorus by restructuring soil type-dependent microbial functional networks, connecting PGRs-induced shifts with microbial phosphorus cycling mechanisms. These findings facilitate the targeted use of PGRs to optimize microbial-driven phosphorus efficiency in strategies for sustainable phosphorus management in diverse agricultural soils. Full article
(This article belongs to the Section Innovative Cropping Systems)
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16 pages, 7782 KB  
Article
Lactobacillus plantarum-Derived Inorganic Polyphosphate Regulates Immune Function via Inhibiting M1 Polarization and Resisting Oxidative Stress in Macrophages
by Shuzhen Li, Aijuan Zheng, Zhimin Chen, Xiaoying Wang, Jiang Chen, Zhiheng Zou and Guohua Liu
Antioxidants 2025, 14(4), 428; https://doi.org/10.3390/antiox14040428 - 1 Apr 2025
Cited by 3 | Viewed by 800
Abstract
Inorganic polyphosphate (PolyP) is a high-molecular-weight polymer that plays multiple roles in regulating immune responses. However, the specific anti-inflammatory mechanisms of bacteria-derived PolyP are unclear. In the present study, PolyP was extracted from Lactobacillus plantarum (L. plantarum), and the chain length [...] Read more.
Inorganic polyphosphate (PolyP) is a high-molecular-weight polymer that plays multiple roles in regulating immune responses. However, the specific anti-inflammatory mechanisms of bacteria-derived PolyP are unclear. In the present study, PolyP was extracted from Lactobacillus plantarum (L. plantarum), and the chain length was estimated to be approximately 250 Pi residues. The immune regulatory functions of PolyP were investigated using a lipopolysaccharide (LPS)-induced RAW264.7 cell oxidative stress model, and dexamethasone was used as a positive control. The result revealed that both dexamethasone and PolyP were protective against oxidative stress by inhibiting macrophage M1 polarization and the production of several markers, such as nitric oxide (NO), reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2. In addition, PolyP suppressed inflammation progression by regulating the production of several cytokines, such as interleukin (IL)-1β, interferon (INF)-γ, tumor necrosis factor (TNF)-α, and IL-6, and inhibited the expressions of inhibitory κB kinase (IKK) α, IKKβ, and extracellular regulated protein kinases 2 (ERK2). Conclusively, PolyP derived from L. plantarum has the ability to protect cells from oxidative stress damage by inhibiting M1 polarization in macrophages. These findings provide insights into the function of PolyP and offer support for the potential application of PolyP in immune-related diseases. Full article
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15 pages, 3022 KB  
Article
Zero-Valent Iron-Enhanced Nutrient Removal in Simultaneous Nitrification Denitrification and Phosphorus Removal Process: Performance, Microbial Community and Potential Mechanism
by Ju Zhang, Xiaoling Zhang, Shuting Xie, Shuhan Lei, Wenjuan Yang, Ying Chen, Aixia Chen and Jianqiang Zhao
Water 2024, 16(24), 3666; https://doi.org/10.3390/w16243666 - 19 Dec 2024
Viewed by 1284
Abstract
The efficacy of zero-valent iron (ZVI) for the simultaneous nitrification denitrification and phosphorus removal (SNDPR) process is unclear, although it has been shown in numerous studies to help improve nitrate removal in biological wastewater treatment systems. This study investigated the response of the [...] Read more.
The efficacy of zero-valent iron (ZVI) for the simultaneous nitrification denitrification and phosphorus removal (SNDPR) process is unclear, although it has been shown in numerous studies to help improve nitrate removal in biological wastewater treatment systems. This study investigated the response of the SNDPR process to ZVI addition in an anaerobic/aerobic/anoxic (An/O/A)-sequencing batch reactor (SBR). The results indicated that ZVI addition could promote the removal of phosphorus and total inorganic nitrogen (TIN). The phosphorus removal by ZVI was mainly attributed to iron precipitation due to the in situ oxidation of ZVI by oxygen or nitrate. The TIN removal by ZVI was attributed to the chemical denitrification reaction, which reduces nitrate to nitrite and nitrogen gas. The nanoscale zero-valent iron (nZVI) was more favorable for TIN removal than microscale zero-valent iron (mZVI) in the SNDPR process. The average removal efficiency of PO43−-P and TIN increased from 50.37 ± 7.55% to 99.29 ± 1.24% and 73.15 ± 5.92% to 76.75 ± 5.05% with nZVI addition. The relative abundance of Dechloromonas sp. decreased by 0.65% and that of Nitrospira sp. increased by 3.78% with the addition of ZVI, indicating that ZVI could weaken the activity of polyphosphate-accumulating organisms (PAOs) and promote the activity of nitrite-oxidizing bacteria. These results provide a new and environmentally friendly approach for applying ZVI in SNDPR systems, reducing the dependence on organic carbon sources. Full article
(This article belongs to the Section Wastewater Treatment and Reuse)
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15 pages, 2951 KB  
Article
Role of Polyphosphate as an Inorganic Chaperone to Prevent Protein Aggregation Under Copper Stress in Saccharolobus solfataricus
by José Acevedo-López, Gabriela González-Madrid, Claudio A. Navarro and Carlos A. Jerez
Microorganisms 2024, 12(12), 2627; https://doi.org/10.3390/microorganisms12122627 - 18 Dec 2024
Cited by 1 | Viewed by 882
Abstract
Polyphosphates are biopolymers composed of phosphate monomers linked by high-energy phosphoanhydride bonds. They are present across all life domains, serving as a source of energy, metal chelators, and playing a crucial role in stress defense. In Escherichia coli, polyphosphates also function as [...] Read more.
Polyphosphates are biopolymers composed of phosphate monomers linked by high-energy phosphoanhydride bonds. They are present across all life domains, serving as a source of energy, metal chelators, and playing a crucial role in stress defense. In Escherichia coli, polyphosphates also function as inorganic molecular chaperones. The present study aims to investigate whether polyphosphate serves a similar chaperone function in archaea, using Saccharolobus solfataricus as a model organism. To this end, polyphosphate was extracted and quantified, the ADP/ATP ratio was determined, insoluble protein extracts were analyzed at different time points after copper exposure, and qPCR was performed to measure the expression of stress-related genes. PolyP was extracted after exposing the archaeon S. solfataricus to different copper concentrations. We determined that polyP degradation is directly correlated with metal concentration. At the minimum inhibitory concentration (MIC) of 2 mM Cu2+, polyP degradation stabilized 2 h after exposure and showed no recovery even after 24 h. The ADP/ATP ratio was measured and showed differences in the presence or absence of polyP. The analysis of proteins precipitated under copper stress showed a higher proportion of insoluble proteins at an elevated metal concentration. On the other hand, increased protein precipitation was detected in the absence of polyP. Gene expression analysis via qPCR was conducted to assess the expression of genes involved in chaperone and chaperonin production, copper resistance, oxidative stress response, and phosphate metabolism under prolonged copper exposure, both in the presence and absence of polyP. The results indicated an upregulation of all the chaperonins measured in the presence of polyP. Interestingly, just some of these genes were upregulated in polyP’s absence. Despite copper stress, there was no upregulation of superoxide dismutase in our conditions. These results highlight the role of polyP in the copper stress response in S. solfataricus, particularly to prevent protein precipitation, likely due to its function as an inorganic chaperone. Additionally, the observed protein precipitation could be attributable to interactions between copper and some amino acids on the protein structures rather than oxidative stress induced by copper exposure, as previously described in E. coli. Our present findings provide new insights into the protective role of polyP as an inorganic chaperone in S. solfataricus and emphasize its importance in maintaining cellular homeostasis under metal stress conditions. Full article
(This article belongs to the Section Microbial Biotechnology)
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15 pages, 2681 KB  
Article
Ammonium Polyphosphate Promotes Maize Growth and Phosphorus Uptake by Altering Root Properties
by Siqi Dong, Asante-Badu Bismark, Songsong Li, Qiang Gao, Xue Zhou and Cuilan Li
Plants 2024, 13(23), 3407; https://doi.org/10.3390/plants13233407 - 4 Dec 2024
Cited by 1 | Viewed by 1442
Abstract
Phosphorus (P) is an essential nutrient for maize growth, significantly affecting both yield and quality. Despite the typically high concentration of available P in black soils, the efficiency of crop uptake and utilization remains relatively low. This study aimed to evaluate the effects [...] Read more.
Phosphorus (P) is an essential nutrient for maize growth, significantly affecting both yield and quality. Despite the typically high concentration of available P in black soils, the efficiency of crop uptake and utilization remains relatively low. This study aimed to evaluate the effects of different P fertilizers on maize yield, root growth parameters, and P use efficiency to identify strategies for optimizing P management in black soil regions. Field experiment results indicated that the combination of ammonium polyphosphate (APP) with other P fertilizers led to variations in yield and P fertilizer absorption efficiency. Various P fertilizers were tested, including diammonium phosphate (DAP), ammonium polyphosphate (APP), fused calcium magnesium phosphate (FCMP), a combination of DAP and FCMP (DAP+FCMP), and a control with no phosphate (CK). The results indicated that P application significantly increased maize yield, with APP (171.8 g/plant) outperforming other P application treatments. Different P fertilizer types significantly affect soil P content and the composition of P fractions. APP significantly increased both the total P (TP) and the proportion of inorganic P (Pi). Furthermore, APP application significantly improved root length (RL), surface area (SAR), and root activity (RA) compared to CK, leading to enhanced nutrient absorption. APP also significantly increased P uptake and utilization (REp, FPp, AEp, PHI, and PAC). In summary, by optimizing plant biomass and P uptake, APP can directly and indirectly influence maize yield. Improving rhizosphere properties through the selection of suitable fertilizer types can enhance fertilizer use efficiency and increase maize production. Full article
(This article belongs to the Special Issue Soil Fertility Management for Plant Growth and Development)
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18 pages, 2208 KB  
Article
Ppn2 Polyphosphatase Improves the Ability of S. cerevisiae to Grow in Mild Alkaline Medium
by Irina A. Eliseeva, Lubov Ryazanova, Larisa Ledova, Anton Zvonarev, Airat Valiakhmetov, Maria Suntsova, Aleksander Modestov, Anton Buzdin, Dmitry N. Lyabin, Ivan V. Kulakovskiy and Tatiana Kulakovskaya
J. Fungi 2024, 10(11), 797; https://doi.org/10.3390/jof10110797 - 16 Nov 2024
Cited by 1 | Viewed by 1342
Abstract
Inorganic polyphosphates and respective metabolic pathways and enzymes are important factors for yeast active growth in unfavorable conditions. However, particular proteins of polyphosphate metabolism remain poorly explored in this context. Here we report biochemical and transcriptomic characterization of the CRN/PPN2 yeast strain (derived [...] Read more.
Inorganic polyphosphates and respective metabolic pathways and enzymes are important factors for yeast active growth in unfavorable conditions. However, particular proteins of polyphosphate metabolism remain poorly explored in this context. Here we report biochemical and transcriptomic characterization of the CRN/PPN2 yeast strain (derived from Ppn1-lacking CRN strain) overexpressing poorly studied Ppn2 polyphosphatase. We showed that Ppn2 overexpression significantly reduced lag phase in the alkaline medium presumably due to the ability of Ppn2 to efficiently hydrolyze inorganic polyphosphates and thus neutralize hydroxide ions in the cell. With RNA-Seq, we compared the molecular phenotypes of CRN/PPN2 and its parent CRN strain grown in YPD or alkaline medium and detected transcriptomic changes induced by Ppn2 overexpression and reflecting the adaptation to alkaline conditions. The core set of upregulated genes included several genes with a previously unknown function. Respective knockout strains (∆ecm8, ∆yol160w, ∆cpp3, ∆ycr099c) exhibited defects of growth or cell morphology in the alkaline medium, proving the functional involvement of the respective proteins in sustaining growth in alkaline conditions. Full article
(This article belongs to the Special Issue Stress Research in Filamentous Fungi and Yeasts)
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23 pages, 3064 KB  
Article
Inorganic Polyphosphate Promotes Colorectal Cancer Growth via TRPM8 Receptor Signaling Pathway
by Valentina Arrè, Francesco Balestra, Rosanna Scialpi, Francesco Dituri, Rossella Donghia, Sergio Coletta, Dolores Stabile, Antonia Bianco, Leonardo Vincenti, Salvatore Fedele, Chen Shen, Giuseppe Pettinato, Maria Principia Scavo, Gianluigi Giannelli and Roberto Negro
Cancers 2024, 16(19), 3326; https://doi.org/10.3390/cancers16193326 - 28 Sep 2024
Cited by 2 | Viewed by 1915
Abstract
Background: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds [...] Read more.
Background: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration. Results: In this study, we tested the role of iPolyP on CRC proliferation, using in vitro and ex vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues, derived from affected individuals enrolled in this study, compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, a well-characterized Na+ and Ca2+ ion channel often overexpressed in CRC and linked with poor prognosis, thus promoting CRC cell proliferation. The pharmacological inhibition of TRPM8 or RNA interference experiments performed in established CRC cell lines, such as Caco-2 and SW620, showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes the Cyclin B protein. In vitro 2D and 3D data reflected the ex vivo results, obtained by the generation of CRC-derived organoids, which increased in size. Conclusions: These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation. Full article
(This article belongs to the Section Cancer Biomarkers)
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11 pages, 4312 KB  
Article
Inorganic Polyphosphate Is in the Surface of Trypanosoma cruzi but Is Not Significantly Secreted
by Logan P. Crowe, Anna Gioseffi, Mayara S. Bertolini and Roberto Docampo
Pathogens 2024, 13(9), 776; https://doi.org/10.3390/pathogens13090776 - 9 Sep 2024
Cited by 2 | Viewed by 1510
Abstract
Trypanosoma cruzi is the etiologic agent of Chagas disease, an infection that can lead to the development of cardiac fibrosis, which is characterized by the deposition of extracellular matrix (ECM) components in the interstitial region of the myocardium. The parasite itself can induce [...] Read more.
Trypanosoma cruzi is the etiologic agent of Chagas disease, an infection that can lead to the development of cardiac fibrosis, which is characterized by the deposition of extracellular matrix (ECM) components in the interstitial region of the myocardium. The parasite itself can induce myofibroblast differentiation of cardiac fibroblast in vitro, leading to increased expression of ECM. Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate that can also induce myofibroblast differentiation and deposition of ECM components and is highly abundant in T. cruzi. PolyP can modify proteins post-translationally by non-enzymatic polyphosphorylation of lysine residues of poly-acidic, serine-(S) and lysine (K)-rich (PASK) motifs. In this work, we used a bioinformatics screen and identified the presence of PASK domains in several surface proteins of T. cruzi. We also detected polyP in the external surface of its different life cycle stages and confirmed the stimulation of host cell fibrosis by trypomastigote infection. However, we were not able to detect significant secretion of the polymer or activation of transforming growth factor beta (TGF-β), an important factor for the generation of fibrosis by inorganic polyP- or trypomastigote-conditioned medium. Full article
(This article belongs to the Special Issue Trypanosoma cruzi Infection: Cellular and Molecular Basis)
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16 pages, 5063 KB  
Article
Quantitative Analysis of Rhodobacter sphaeroides Storage Organelles via Cryo-Electron Tomography and Light Microscopy
by Daniel Parrell, Joseph Olson, Rachelle A. Lemke, Timothy J. Donohue and Elizabeth R. Wright
Biomolecules 2024, 14(8), 1006; https://doi.org/10.3390/biom14081006 - 14 Aug 2024
Viewed by 2295
Abstract
Bacterial cytoplasmic organelles are diverse and serve many varied purposes. Here, we employed Rhodobacter sphaeroides to investigate the accumulation of carbon and inorganic phosphate in the storage organelles, polyhydroxybutyrate (PHB) and polyphosphate (PP), respectively. Using cryo-electron tomography (cryo-ET), these organelles were observed to [...] Read more.
Bacterial cytoplasmic organelles are diverse and serve many varied purposes. Here, we employed Rhodobacter sphaeroides to investigate the accumulation of carbon and inorganic phosphate in the storage organelles, polyhydroxybutyrate (PHB) and polyphosphate (PP), respectively. Using cryo-electron tomography (cryo-ET), these organelles were observed to increase in size and abundance when growth was arrested by chloramphenicol treatment. The accumulation of PHB and PP was quantified from three-dimensional (3D) segmentations in cryo-tomograms and the analysis of these 3D models. The quantification of PHB using both segmentation analysis and liquid chromatography and mass spectrometry (LCMS) each demonstrated an over 10- to 20-fold accumulation of PHB. The cytoplasmic location of PHB in cells was assessed with fluorescence light microscopy using a PhaP-mNeonGreen fusion-protein construct. The subcellular location and enumeration of these organelles were correlated by comparing the cryo-ET and fluorescence microscopy data. A potential link between PHB and PP localization and possible explanations for co-localization are discussed. Finally, the study of PHB and PP granules, and their accumulation, is discussed in the context of advancing fundamental knowledge about bacterial stress response, the study of renewable sources of bioplastics, and highly energetic compounds. Full article
(This article belongs to the Special Issue New Insights into the Membranes of Anoxygenic Phototrophic Bacteria)
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17 pages, 778 KB  
Review
An Update on Polyphosphate In Vivo Activities
by Robert Schoeppe, Moritz Waldmann, Henning J. Jessen and Thomas Renné
Biomolecules 2024, 14(8), 937; https://doi.org/10.3390/biom14080937 - 2 Aug 2024
Cited by 9 | Viewed by 3427
Abstract
Polyphosphate (polyP) is an evolutionary ancient inorganic molecule widespread in biology, exerting a broad range of biological activities. The intracellular polymer serves as an energy storage pool and phosphate/calcium ion reservoir with implications for basal cellular functions. Metabolisms of the polymer are well [...] Read more.
Polyphosphate (polyP) is an evolutionary ancient inorganic molecule widespread in biology, exerting a broad range of biological activities. The intracellular polymer serves as an energy storage pool and phosphate/calcium ion reservoir with implications for basal cellular functions. Metabolisms of the polymer are well understood in procaryotes and unicellular eukaryotic cells. However, functions, regulation, and association with disease states of the polymer in higher eukaryotic species such as mammalians are just beginning to emerge. The review summarises our current understanding of polyP metabolism, the polymer’s functions, and methods for polyP analysis. In-depth knowledge of the pathways that control polyP turnover will open future perspectives for selective targeting of the polymer. Full article
(This article belongs to the Special Issue Inorganic Polyphosphate: A Multifaceted Biomolecule)
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2 pages, 146 KB  
Abstract
Deletion of the PHO91 Gene Leads to Impaired Ability to Consume Methanol in Cells of the Methylotrophic Yeast Ogataea Parapolymorpha 
by Vasilina Farofonova, Azamat Karginov, Michael Agaphonov and Tatiana Kulakovskaya
Proceedings 2024, 105(1), 83; https://doi.org/10.3390/proceedings2024105083 - 28 May 2024
Viewed by 577
Abstract
The PHO91 and PHO87 are parts of yeast’s phosphate metabolism system. We investigated the influence of PHO91 deletion on the methanol utilization as a sole carbon source in Ogataea parapolymorpha through comparison of wet biomass, protein content, methanol oxidase (MOX) activity and acid-soluble [...] Read more.
The PHO91 and PHO87 are parts of yeast’s phosphate metabolism system. We investigated the influence of PHO91 deletion on the methanol utilization as a sole carbon source in Ogataea parapolymorpha through comparison of wet biomass, protein content, methanol oxidase (MOX) activity and acid-soluble and acid-insoluble inorganic polyphosphate (polyP) content, while growing on methanol and without any carbon source other than trace amounts from the yeast extract. The Δpho91 strain has a lack of wet biomass, protein content and MOX activity while grown on methanol (as a ΔMOX strain) and has the same numbers as a WT strain in media without methanol. We found two ways of recovering methanol utilizing capabilities for Δpho91 mutant—either adding MOX on plasmid under constitutive promoter control, or adding a Δpho87 mutation. Both Δpho91 + MOX and Δpho91Δpho87 strains showed all the parameters as a WT strain on methanol as a sole carbon source and without methanol addition. Further, we compare the polyP content of the strains in methanol media, media without a sole carbon source and media with glucose. All of the WT, Δpho91 + MOX and Δpho91Δpho87 strains, capable of utilizing methanol, have the Pi, acid-soluble and acid-insoluble polyP at the same levels with some variations. The ΔMOX and Δpho91 strains, despite both not being able to utilize methanol, showed very different levels of Pi and polyP’s, which can be interpreted as different mechanisms of the inner cell, leading to a loss of capability utilizing methanol in both of these strains. Full article
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