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Research Advances in the Mutual Mechanisms Regulating Response of Plant Roots to Phosphate Deficiency and Aluminum Toxicity.
Chen, W, Tang, L, Wang, J, Zhu, H, Jin, J, Yang, J, Fan, W
International journal of molecular sciences. 2022;(3)
Abstract
Low phosphate (Pi) availability and high aluminum (Al) toxicity constitute two major plant mineral nutritional stressors that limit plant productivity on acidic soils. Advances toward the identification of genes and signaling networks that are involved in both stresses in model plants such as Arabidopsis thaliana and rice (Oryza sativa), and in other plants as well have revealed that some factors such as organic acids (OAs), cell wall properties, phytohormones, and iron (Fe) homeostasis are interconnected with each other. Moreover, OAs are involved in recruiting of many plant-growth-promoting bacteria that are able to secrete both OAs and phosphatases to increase Pi availability and decrease Al toxicity. In this review paper, we summarize these mutual mechanisms by which plants deal with both Al toxicity and P starvation, with emphasis on OA secretion regulation, plant-growth-promoting bacteria, transcription factors, transporters, hormones, and cell wall-related kinases in the context of root development and root system architecture remodeling that plays a determinant role in improving P use efficiency and Al resistance on acidic soils.
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The Genetic Basis of Phosphorus Utilization Efficiency in Plants Provide New Insight into Woody Perennial Plants Improvement.
Pan, Y, Song, Y, Zhao, L, Chen, P, Bu, C, Liu, P, Zhang, D
International journal of molecular sciences. 2022;(4)
Abstract
Soil nutrient restrictions are the main environmental conditions limiting plant growth, development, yield, and quality. Phosphorus (P), an essential macronutrient, is one of the most significant factors that vastly restrains the growth and development of plants. Although the total P is rich in soil, its bio-available concentration is still unable to meet the requirements of plants. To maintain P homeostasis, plants have developed lots of intricate responsive and acclimatory mechanisms at different levels, which contribute to administering the acquisition of inorganic phosphate (Pi), translocation, remobilization, and recycling of Pi. In recent years, significant advances have been made in the exploration of the utilization of P in annual plants, while the research progress in woody perennial plants is still vague. In the meanwhile, compared to annual plants, relevant reviews about P utilization in woody perennial plants are scarce. Therefore, based on the importance of P in the growth and development of plants, we briefly reviewed the latest advances on the genetic and molecular mechanisms of plants to uphold P homeostasis, P sensing, and signaling, ion transporting and metabolic regulation, and proposed the possible sustainable management strategies to fasten the P cycle in modern agriculture and new directions for future studies.
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Intracellular phosphate sensing and regulation of phosphate transport systems in plants.
Wang, Z, Kuo, HF, Chiou, TJ
Plant physiology. 2021;(4):2043-2055
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Abstract
Recent research on the regulation of cellular phosphate (Pi) homeostasis in eukaryotes has collectively made substantial advances in elucidating inositol pyrophosphates (PP-InsP) as Pi signaling molecules that are perceived by the SPX (Syg1, Pho81, and Xpr1) domains residing in multiple proteins involved in Pi transport and signaling. The PP-InsP-SPX signaling module is evolutionarily conserved across eukaryotes and has been elaborately adopted in plant Pi transport and signaling systems. In this review, we have integrated these advances with prior established knowledge of Pi and PP-InsP metabolism, intracellular Pi sensing, and transcriptional responses according to the dynamics of cellular Pi status in plants. Anticipated challenges and pending questions as well as prospects are also discussed.
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Vascular Calcification: Key Roles of Phosphate and Pyrophosphate.
Villa-Bellosta, R
International journal of molecular sciences. 2021;(24)
Abstract
Cardiovascular complications due to accelerated arterial stiffening and atherosclerosis are the leading cause of morbimortality in Western society. Both pathologies are frequently associated with vascular calcification. Pathologic calcification of cardiovascular structures, or vascular calcification, is associated with several diseases (for example, genetic diseases, diabetes, and chronic kidney disease) and is a common consequence of aging. Calcium phosphate deposition, mainly in the form of hydroxyapatite, is the hallmark of vascular calcification and can occur in the medial layer of arteries (medial calcification), in the atheroma plaque (intimal calcification), and cardiac valves (heart valve calcification). Although various mechanisms have been proposed for the pathogenesis of vascular calcification, our understanding of the pathogenesis of calcification is far from complete. However, in recent years, some risk factors have been identified, including high serum phosphorus concentration (hyperphosphatemia) and defective synthesis of pyrophosphate (pyrophosphate deficiency). The balance between phosphate and pyrophosphate, strictly controlled by several genes, plays a key role in vascular calcification. This review summarizes the current knowledge concerning phosphate and pyrophosphate homeostasis, focusing on the role of extracellular pyrophosphate metabolism in aortic smooth muscle cells and macrophages.
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Safety and effectiveness of lanthanum carbonate for hyperphosphatemia in chronic kidney disease (CKD) patients: a meta-analysis.
Zhao, L, Liu, A, Xu, G
Renal failure. 2021;(1):1378-1393
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Abstract
OBJECTIVE The aim of this study was to determine the efficacy and safety of lanthanum carbonate (LC) versus calcium salts, non-LC phosphate binders (PBs), sevelamer, or placebo in patients with chronic kidney disease (CKD). MATERIALS AND METHODS A literature search on PubMed, Embase, and Cochrane Library databases was conducted up to 18 June 2021. Data acquisition and quality assessment were performed by two reviewers. Meta-analysis was performed to evaluate the serum biochemical parameters, adverse events, and patient-level outcomes of LC, non-LC PBs, and sevelamer for hyperphosphatemia in patients with CKD. Heterogeneity across studies was assessed utilizing the I2 statistic and Q-test, and a random effect model was selected to calculate the pooled effect size. RESULTS A total of 26 randomized, controlled trials and 3 observational studies were included. Compared to the other groups, better control effect of serum phosphorus (RR = 2.68, p < 0.001), reduction in serum phosphorus (95%CI = -1.93, -0.99; p < 0.001), Ca × P (95%CI = -13.89, -2.99; p = 0.002), serum intact parathyroid hormone levels (95%CI = -181.17, -3.96, p = 0.041) were found in LC group. Besides, reduced risk of various adverse effects, such as hypotension, abdominal pain, diarrhea, dyspepsia, and a score of coronary artery calcification were identified with LC in comparison to calcium salt, non-LC PBs, or placebo group. Significantly lower risk in mortality with LC treatment vs. non-LC PBs was observed, while no significant difference was identified between LC and calcium salt groups. CONCLUSION LC might be an alternative treatment for hyperphosphatemia in patients with CKD considering its comprehensive curative effect.
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Phosphate and fibroblast growth factor 23 in diabetes.
van der Vaart, A, Yeung, SMH, van Dijk, PR, Bakker, SJL, de Borst, MH
Clinical science (London, England : 1979). 2021;(14):1669-1687
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Abstract
Diabetes is associated with a strongly elevated risk of cardiovascular disease, which is even more pronounced in patients with diabetic nephropathy. Currently available guideline-based efforts to correct traditional risk factors are only partly able to attenuate this risk, underlining the urge to identify novel treatment targets. Emerging data point towards a role for disturbances in phosphate metabolism in diabetes. In this review, we discuss the role of phosphate and the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) in diabetes. We address deregulations of phosphate metabolism in patients with diabetes, including diabetic ketoacidosis. Moreover, we discuss potential adverse consequences of these deregulations, including the role of deregulated phosphate and glucose as drivers of vascular calcification propensity. Finally, we highlight potential treatment options to correct abnormalities in phosphate and FGF23. While further studies are needed to more precisely assess their clinical impact, deregulations in phosphate and FGF23 are promising potential target in diabetes and diabetic nephropathy.
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Inflammation: a putative link between phosphate metabolism and cardiovascular disease.
Voelkl, J, Egli-Spichtig, D, Alesutan, I, Wagner, CA
Clinical science (London, England : 1979). 2021;(1):201-227
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Abstract
Dietary habits in the western world lead to increasing phosphate intake. Under physiological conditions, extraosseous precipitation of phosphate with calcium is prevented by a mineral buffering system composed of calcification inhibitors and tight control of serum phosphate levels. The coordinated hormonal regulation of serum phosphate involves fibroblast growth factor 23 (FGF23), αKlotho, parathyroid hormone (PTH) and calcitriol. A severe derangement of phosphate homeostasis is observed in patients with chronic kidney disease (CKD), a patient collective with extremely high risk of cardiovascular morbidity and mortality. Higher phosphate levels in serum have been associated with increased risk for cardiovascular disease (CVD) in CKD patients, but also in the general population. The causal connections between phosphate and CVD are currently incompletely understood. An assumed link between phosphate and cardiovascular risk is the development of medial vascular calcification, a process actively promoted and regulated by a complex mechanistic interplay involving activation of pro-inflammatory signalling. Emerging evidence indicates a link between disturbances in phosphate homeostasis and inflammation. The present review focuses on critical interactions of phosphate homeostasis, inflammation, vascular calcification and CVD. Especially, pro-inflammatory responses mediating hyperphosphatemia-related development of vascular calcification as well as FGF23 as a critical factor in the interplay between inflammation and cardiovascular alterations, beyond its phosphaturic effects, are addressed.
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The mutual interactions of RNA, counterions and water - quantifying the electrostatics at the phosphate-water interface.
Fingerhut, BP
Chemical communications (Cambridge, England). 2021;(96):12880-12897
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Abstract
The structure and dynamics of polyanionic biomolecules, like RNA, are decisively determined by their electric interactions with the water molecules and the counterions in the environment. The solvation dynamics of the biomolecules involves a subtle balance of non-covalent and many-body interactions with structural fluctuations due to thermal motion occurring in a femto- to subnanosecond time range. This complex fluctuating many particle scenario is crucial in defining the properties of biological interfaces with far reaching significance for the folding of RNA structures and for facilitating RNA-protein interactions. Given the inherent complexity, suited model systems, carefully calibrated and benchmarked by experiments, are required to quantify the relevant interactions of RNA with the aqueous environment. In this feature article we summarize our recent progress in the understanding of the electrostatics at the biological interface of double stranded RNA (dsRNA) and transfer RNA (tRNA). Dimethyl phosphate (DMP) is introduced as a viable and rigorously accessible model system allowing the interaction strength with water molecules and counterions, their relevant fluctuation timescales and the spatial reach of interactions to be established. We find strong (up to ≈90 MV cm-1) interfacial electric fields with fluctuations extending up to ≈20 THz and demonstrate how the asymmetric stretching vibration νAS(PO2)- of the polarizable phosphate group can serve as the most sensitive probe for interfacial interactions, establishing a rigorous link between simulations and experiment. The approach allows for the direct interfacial observation of interactions of biologically relevant Mg2+ counterions with phosphate groups in contact pair geometries via the rise of a new absorption band imposed by exchange repulsion interactions at short interatomic distances. The systematic extension to RNA provides microscopic insights into the changes of the hydration structure that accompany the temperature induced melting of the dsRNA double helix and quantify the ionic interactions in the folded tRNA. The results show that pairs of negatively charged phosphate groups and Mg2+ ions represent a key structural feature of RNA embedded in water. They highlight the importance of binding motifs made of contact pairs in the electrostatic stabilization of RNA structures that have a strong impact on the surface potential and enable the fine tuning of the local electrostatic properties which are expected to be relevant for mediating the interactions between biomolecules.
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Cycles, sources, and sinks: Conceptualizing how phosphate balance modulates carbon flux using yeast metabolic networks.
Gupta, R, Laxman, S
eLife. 2021
Abstract
Phosphates are ubiquitous molecules that enable critical intracellular biochemical reactions. Therefore, cells have elaborate responses to phosphate limitation. Our understanding of long-term transcriptional responses to phosphate limitation is extensive. Contrastingly, a systems-level perspective presenting unifying biochemical concepts to interpret how phosphate balance is critically coupled to (and controls) metabolic information flow is missing. To conceptualize such processes, utilizing yeast metabolic networks we categorize phosphates utilized in metabolism into cycles, sources and sinks. Through this, we identify metabolic reactions leading to putative phosphate sources or sinks. With this conceptualization, we illustrate how mass action driven flux towards sources and sinks enable cells to manage phosphate availability during transient/immediate phosphate limitations. We thereby identify how intracellular phosphate availability will predictably alter specific nodes in carbon metabolism, and determine signature cellular metabolic states. Finally, we identify a need to understand intracellular phosphate pools, in order to address mechanisms of phosphate regulation and restoration.
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New Developments in the Treatment of X-Linked Hypophosphataemia: Implications for Clinical Management.
Saraff, V, Nadar, R, Högler, W
Paediatric drugs. 2020;(2):113-121
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Abstract
X-linked hypophosphataemia (XLH) is due to mutations in phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and represents the most common heritable form of rickets. In this condition, the hormone fibroblast growth factor 23 (FGF23) is produced in excessive amounts for still unknown reasons, and causes renal phosphate wasting and suppression of 1,25-dihydroxyvitamin D, leading to low serum phosphate concentrations. Prolonged hypophosphataemia decreases apoptosis of hypertrophic chondrocytes in growth plates (causing rickets) and decreases mineralisation of existing bone (causing osteomalacia). In contrast to historical conventional treatment with oral phosphate supplements and active vitamin D for the last 50 years, the new anti-FGF23 antibody treatment (burosumab) targets the primary pathology by blocking FGF23, thereby restoring phosphate homeostasis. In this review, we describe the changes in treatment monitoring, treatment targets and long-term treatment goals, including future opportunities and challenges in the treatment of XLH in children.