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Silver jubilee: 25 years of the first demonstration of the direct effect of phosphate on the parathyroid cell.
Bover, J, Trinidad, P, Jara, A, Soler-Majoral, J, Martín-Malo, A, Torres, A, Frazão, J, Ureña, P, Dusso, A, Arana, C, et al
Nefrologia. 2022;(6):645-655
Abstract
Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43-), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43- in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43- on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43- overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role.
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2.
Role of Nitrate Reductase in NO Production in Photosynthetic Eukaryotes.
Tejada-Jimenez, M, Llamas, A, Galván, A, Fernández, E
Plants (Basel, Switzerland). 2019;(3)
Abstract
Nitric oxide is a gaseous secondary messenger that is critical for proper cell signaling and plant survival when exposed to stress. Nitric oxide (NO) synthesis in plants, under standard phototrophic oxygenic conditions, has long been a very controversial issue. A few algal strains contain NO synthase (NOS), which appears to be absent in all other algae and land plants. The experimental data have led to the hypothesis that molybdoenzyme nitrate reductase (NR) is the main enzyme responsible for NO production in most plants. Recently, NR was found to be a necessary partner in a dual system that also includes another molybdoenzyme, which was renamed NO-forming nitrite reductase (NOFNiR). This enzyme produces NO independently of the molybdenum center of NR and depends on the NR electron transport chain from NAD(P)H to heme. Under the circumstances in which NR is not present or active, the existence of another NO-forming system that is similar to the NOS system would account for NO production and NO effects. PII protein, which senses and integrates the signals of the C⁻N balance in the cell, likely has an important role in organizing cell responses. Here, we critically analyze these topics.
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3.
Integral pharmacological management of bone mineral disorders in chronic kidney disease (part II): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification.
Bover, J, Ureña-Torres, P, Lloret, MJ, Ruiz, C, DaSilva, I, Diaz-Encarnacion, MM, Mercado, C, Mateu, S, Fernández, E, Ballarin, J
Expert opinion on pharmacotherapy. 2016;(10):1363-73
Abstract
INTRODUCTION Chronic kidney disease-mineral and bone disorders (CKD-MBD) are associated with costly complications and dismal hard-outcomes. AREAS COVERED In two comprehensive articles we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (part 1) and hyperparathyroidism (this part 2), taking into account CKD-accelerated cardiovascular calcification (CVC) processes. EXPERT OPINION Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Here, initial guidance to control hyperparathyroidism is provided, taking into account the presence/absence of CVC. We include also measures for patients at risk of adynamic bone disease or suffering from calciphylaxis. Many epidemiological studies (relating to vitamin D) and thorough analyses of recent randomized clinical trials (of cinacalcet) point towards benefits of attempting to improve biochemical parameters while trying to, at least, avoid progression of CVC by more rational use of intestinal P-binders and low-dose vitamin D derivatives and/or calcimimetics. This approach does not seem to be far away from significantly improving hard-outcomes, at least in the dialysis population. The availability of new drugs and the performance of randomized clinical trials should ultimately lead to define earlier, clearer, and more cost-effective patient stratification and biochemical targets with consequent significant clinical improvements.
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4.
Integral pharmacological management of bone mineral disorders in chronic kidney disease (part I): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification.
Bover, J, Ureña-Torres, P, Lloret, MJ, Ruiz-García, C, DaSilva, I, Diaz-Encarnacion, MM, Mercado, C, Mateu, S, Fernández, E, Ballarin, J
Expert opinion on pharmacotherapy. 2016;(9):1247-58
Abstract
INTRODUCTION Chronic kidney disease-mineral and bone disorders (CKD-MBD), involving a triad of laboratory and bone abnormalities, and tissue calcifications, are associated with dismal hard-outcomes. AREAS COVERED In two comprehensive articles, we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (this part 1) and hyperparathyroidism (part 2), taking into account CKD-accelerated atheromatosis/atherosclerosis and/or cardiovascular calcification (CVC) processes. EXPERT OPINION Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Individualization of treatment with P-binders and combinations of anti-parathyroid agents may improve biochemical control with lower incidence of undesirable effects. Isolated biochemical parameters do not accurately reflect calcium or P load or bone activity and do not stratify high cardiovascular risk patients with CKD. Initial guidance is provided on reasonable therapeutic strategies which consider the presence of CVC. This part reflects that although there is not an absolute evidence, many studies point to the need to improve P imbalance while trying to, at least, avoid progression of CVC by restriction of Ca-based P-binders if economically feasible. The availability of new drugs (i.e. inhibitors of intestinal transporters), and studies including early CKD should ultimately lead to clearer and more cost/effective clinical targets for CKD-MBD.
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5.
Molybdenum metabolism in plants.
Tejada-Jiménez, M, Chamizo-Ampudia, A, Galván, A, Fernández, E, Llamas, Á
Metallomics : integrated biometal science. 2013;(9):1191-203
Abstract
The viability of plants relies on molybdenum, which after binding to the organic moiety of molybdopterin forms the molybdenum cofactor (Moco) and acquires remarkable redox properties. Moco is in the active site of critical molybdoenzymes, which use to work as small electron transport chains and participate in N and S metabolism, hormone biosynthesis, toxic compound transformations and other important processes not only in plants but also in all the other kingdoms of life. Molybdate metabolism in plants is reviewed here, with special attention to two main aspects, the different molybdate transporters that with a very high affinity participate in molybdenum acquisition and the recently discovered Moco enzyme amidoxime-reducing component. Their functionality is starting to be understood.
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6.
Molybdenum metabolism in the alga Chlamydomonas stands at the crossroad of those in Arabidopsis and humans.
Llamas, A, Tejada-Jiménez, M, Fernández, E, Galván, A
Metallomics : integrated biometal science. 2011;(6):578-90
Abstract
Molybdenum (Mo) is a very scarce element whose function is fundamental in living beings within the active site of Mo-oxidoreductases, playing key roles in the metabolism of N, S, purines, hormone biosynthesis, transformation of drugs and xenobiotics, etc. In eukaryotes, each step from Mo acquisition until its incorporation into a biologically active molybdenum cofactor (Moco) together with the assembly of this Moco in Mo-enzymes is almost understood. The deficiency in function of a particular molybdoenzyme can be critical for the survival of the organism dependent on the pathway involved. However, incapacity in forming a functional Moco has a pleiotropic effect in the different processes involving this cofactor. A detailed overview of Mo metabolism: (a) specific transporters for molybdate, (b) the universal biosynthesis pathway for Moco from GTP, (c) Moco-carrier and Moco-binding proteins for Moco transfer and (d) Mo-enzymes, is analyzed in light of recent findings and three systems are compared, the unicellular microalga Chlamydomonas, the plant Arabidopsis and humans.
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7.
Homeostasis of the micronutrients Ni, Mo and Cl with specific biochemical functions.
Tejada-Jiménez, M, Galván, A, Fernández, E, Llamas, A
Current opinion in plant biology. 2009;(3):358-63
Abstract
Homeostasis of three elements nickel, molybdenum and chloride is analysed. These micronutrients, at amounts varying in orders of magnitude, fulfil important cell functions. In general terms, cells use similar strategies to ensure that the elements are within physiological ranges avoiding high toxic concentrations. These strategies correspond to specific carriers, channels and pumps, intermediate steps (chelating/sequestration/binding/metabolic conversion/storage), final steps related to specific enzyme functionality and putative sensing proteins. Single cell homeostasis, coordinated with an efficient redistribution by xylem loading, ensures in turn homeostasis at the whole plant level. Recent advances are based on the molecular identification of some key components.
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8.
[Prevention and treatment of renal osteodystrophy: present and future].
Fernández, E, Craver, L
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2006;:19-27
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9.
Overview of renal bone disease: causes of treatment failure, clinical observations, the changing pattern of bone lesions, and future therapeutic approach.
Llach, F, Fernández, E
Kidney international. Supplement. 2003;(87):S113-9