Perspectives on the evolution of aquaporin superfamily.
Abstract Aquaporins (AQPs) belong to a transmembrane protein superfamily composed of an internal repeat of a three membrane-spanning domain and each has a highly conserved NPA box. Based on the more variable carboxyl-terminal NPA box, AQPs can be divided into three subfamilies: (1) glycerol-channel aquaglyceroporin (gAQP) (2) water-selective AQP (wAQP), and (3) deviated superaquaporin (sAQP) in the order of passible evolution. This classification has functional and localization relevance: most wAQPs transports water selectively whereas gAQPs and sAQPs also transport small molecules with sAQPs mostly localized insi...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Ishibashi K, Tanaka Y, Morishita Y Tags: Vitam Horm Source Type: research

Regulation of aquaporin-2 by RNA interference.
Abstract MicroRNAs (miRNAs) are short non-coding RNAs that interact with 3'-untranslated regions of mRNAs. miRNAs modulate gene expression by regulating mRNA translation and provide novel insights into the complex regulation of protein expression and function. In this chapter, we describe the general features of RNA interference, identification of miRNAs, and interaction of miRNAs with their target genes. In particular, we have shown that several miRNAs are responsive to arginine vasopressin or aldosterone stimulation in mouse cortical collecting duct mpkCCD cells. Moreover, we identified both miR-32 and miR-137 a...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Jung HJ, Park EJ, Choi HJ, Kwon TH Tags: Vitam Horm Source Type: research

Aquaporin regulation: Lessons from secretory vesicles.
Abstract Secretory vesicle swelling has been demonstrated to be a requirement in cell secretion. In the past 25 years, the quest to elucidate the molecular mechanism of secretory vesicle swelling, serendipitously revealed the presence of water channels or aquaporins at the secretory vesicle membrane and their involvement in rapid gaiting of water into secretory vesicles and their swelling during secretion. These studies further provided an understanding of aquaporin regulation at the secretory vesicle membrane. Secretory vesicles within live cells, isolated secretory vesicles, single vesicle electrophysiological p...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Jena BP Tags: Vitam Horm Source Type: research

CFTR regulation of aquaporin-mediated water transport.
Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel responsible for the direct transport of bicarbonate and chloride. CFTR-dependent ionic transport is crucial for pH regulation and fluid homeodynamics among epithelial surfaces. Particularly, CFTR performs an essential role in the male reproductive tract, which requires a tight regulation of water and electrolytes in order to produce healthy spermatozoa. The absence or malfunction of CFTR results in cystic fibrosis, the most common lethal disease among Caucasians, that is characterized by an impaired fluid and ionic homeosta...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Carrageta DF, Bernardino RL, Alves MG, Oliveira PF Tags: Vitam Horm Source Type: research

Glucocorticoid gene regulation of aquaporin-7.
Villarroya F, Varela-Echavarria A, Mora O Abstract AQP7 is the primary glycerol transporter in white (WAT) and brown (BAT) adipose tissues. There are immediate and quantitatively important actions of cortisone over the expression of AQP7 in murine and human adipocytes. Short-term response (minutes) of cortisone treatment result in an mRNA overexpression in white and brown differentiated adipocytes (between 1.5 and 6 folds). Conversely, long-term response (hours or days) result in decreased mRNA expression. The effects observed on AQP7 mRNA expression upon cortisone treatment in brown and white differentiated adipo...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: González-Dávalos L, Álvarez-Pérez M, Quesada-López T, Cereijo R, Campderrós L, Piña E, Shimada A, Villarroya F, Varela-Echavarria A, Mora O Tags: Vitam Horm Source Type: research

Modulation by steroid hormones and other factors on the expression of aquaporin-1 and aquaporin-5.
PMID: 32061342 [PubMed - in process] (Source: Vitamins and Hormones)
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Skowronska A, Tanski D, Jaskiewicz L, Skowronski MT Tags: Vitam Horm Source Type: research

Estrogen regulates aquaporin-2 expression in the kidney.
ard R Abstract Estrogens are primarily identified as sex hormones that, for a long time, have been known as important regulators of female reproductive physiology. However, our understanding of the role of estrogens has changed over the past years. It is now well accepted that estrogens are also involved in other physiological and pathological processes in both genders. This is due to the fact that estrogen can act both local as well as on a systemic level. Next to its role in reproductive physiology, there is accumulating evidence that estrogen influences multiple systems involved in water homeostasis. This chapt...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Tingskov SJ, Mutsaers HAM, Nørregaard R Tags: Vitam Horm Source Type: research

Hormonal regulation of aquaporins in fishes.
Abstract Comparative studies over the last two decades have revealed that fishes leverage aquaporins (AQPs) to facilitate the movements of water, small non-ionic solutes, and gases across cell membranes. Accordingly, AQPs are expressed in tissues responsible for maintaining hydromineral balance of the whole organism. In teleost fishes, threats to hydromineral balance imposed by fluctuations in environmental salinity are met with the activation of multiple endocrine axes. This chapter first discusses recent advances in our understanding of how hormones control the expression of AQPs in tissues that support hydromin...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Breves JP Tags: Vitam Horm Source Type: research

Calcium sensing receptor exerts a negative regulatory action toward vasopressin-induced aquaporin-2 expression and trafficking in renal collecting duct.
Abstract Vasopressin (AVP) plays a major role in the regulation of water homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. An increase in plasma sodium concentration stimulates AVP release, which in turn promotes water reabsorption. Upon binding to the V2 receptors in the renal collecting duct, AVP induces the expression and apical membrane insertion of the aquaporin-2 (AQP2) water channels and subsequent water reabsorption. AVP regulates two independent mechanisms: the short-term regulation of AQP2 trafficking and long-term regulation of the total abundance of the AQP2 protein in the...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Ranieri M, Di Mise A, Tamma G, Valenti G Tags: Vitam Horm Source Type: research

Structure and dynamics of aquaporin-1.
Abstract Structural response of a AQP1 is examined by a coarse-grained model with a phenomenological interaction potential with a knowledge-based residue-residue interaction (derived from an ensemble of protein structures in PDB). The thermal response of the protein chain exhibits an unexpected characteristics in its native phase where the radius of gyration of the protein decreases on raising the temperature. The radius of gyration of AQP1 increases on increasing the temperature before saturating to a random-coil morphology in denatured phase at high temperatures. Three regions of persistent globularization are i...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Rangubpit W, Sompornpisut P, Pandey R Tags: Vitam Horm Source Type: research

Aquaporins and placenta.
miano AE, Sánchez-Margalet V Abstract Water is the major component of cells and tissues. The fetal body consists of about 70-90% water and its fluid balance is dependent on the mother. In fact, abortion, premature birth, amniotic fluid volume abnormality, malformation and fetal growth restrictions might result when the homeostasis of the maternal-fetal fluid exchange is disrupted. Thus, maternal-fetal fluid balance is critical during pregnancy. In this sense, several mechanisms, including aquaporins (AQPs) have been reported to play important roles in maternal-fetal fluid balance. AQPs are small membrane pr...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Pérez-Pérez A, Vilariño-García T, Dietrich V, Guadix P, Dueñas JL, Varone CL, Damiano AE, Sánchez-Margalet V Tags: Vitam Horm Source Type: research

Aquaporins during pregnancy.
Abstract Aquaporins (AQPs) are water channels proteins that facilitate water flux across cell membranes in response to osmotic gradients. Despite of the differences in the mammalian placentas, the conserved combination of AQPs expressed in placental and fetal membranes throughout gestation suggests that these proteins may be important in the regulation of fetal water homeostasis. Thus, AQPs may regulate the amniotic fluid volume and participate in the trans-placental transfer of water. Apart from their classical roles, recent studies have revealed that placental AQPs may also cooperate in cellular processes such a...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Damiano AE Tags: Vitam Horm Source Type: research

Selectivity and transport in aquaporins from molecular simulation studies.
Abstract The transport of water through aquaporins is a dynamic process that involves rapid movement of a chain of water molecules through the pore of the aquaporin. Structures of aquaporins solved using X-ray crystallography have provided some insights into how water is transported through these channels, and how certain structural features of the pore might help exclude other solutes from passing through the pore. However, such techniques provide only a static picture, and a dynamic picture of the transport and selectivity mechanism at work in aquaporins is possible with molecular dynamics (MD) simulations. In M...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Padhi S, Priyakumar UD Tags: Vitam Horm Source Type: research

Aquaporin regulation in metabolic organs.
Abstract Aquaporins (AQPs) are a family of 13 small trans-membrane proteins, which facilitate shuttling of glycerol, water and urea. The peculiar role of AQPs in glycerol transport makes them attractive targets in metabolic organs since glycerol represents the backbone of triglyceride synthesis. Importantly, AQPs are known to be regulated by various nuclear receptors which in turn govern lipid and glucose metabolism as well as inflammatory cascades. Here, we review the role of AQPs regulation in metabolic organs exploring their physiological impact in health and disease. PMID: 32061350 [PubMed - in process] (...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Tardelli M, Stulnig TM Tags: Vitam Horm Source Type: research

Phosphorylation of human AQP2 and its role in trafficking.
d S Abstract Human Aquaporin 2 (AQP2) is a membrane-bound water channel found in the kidney collecting duct whose regulation by trafficking plays a key role in regulating urine volume. AQP2 trafficking is tightly controlled by the pituitary hormone arginine vasopressin (AVP), which stimulates translocation of AQP2 residing in storage vesicles to the apical membrane. The AVP-dependent translocation of AQP2 to and from the apical membrane is controlled by multiple phosphorylation sites in the AQP2 C-terminus, the phosphorylation of which alters its affinity to proteins within the cellular membrane protein traffickin...
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Törnroth-Horsefield S Tags: Vitam Horm Source Type: research

Preface.
PMID: 32061352 [PubMed - in process] (Source: Vitamins and Hormones)
Source: Vitamins and Hormones - February 19, 2020 Category: Endocrinology Authors: Litwack G Tags: Vitam Horm Source Type: research

Evolution of proopiomelanocortin.
er JM Abstract Proopiomelanocortin (POMC) belongs to the opioid/orphanin gene family whose peptide precursors include either opioid (YGGF) or the orphanin/nociceptin core sequences (FGGF). In addition to POMC the family includes the proenkephalin (PENK), prodynorphin (PDYN), and nociceptin/proorphanin (PNOC) precursors. The opioid core sequence in POMC is incorporated by the β-endorphin that occupies the C-terminal region but this propeptide also exhibits at least two "alien" melanocortin core sequences (HFRW). An ACTH/MSH fragment merged into the opioid fragment not earlier than the two tetraploidi...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Rocha A, Godino-Gimeno A, Cerdá-Reverter JM Tags: Vitam Horm Source Type: research

Enkephalinase regulation.
Banegas I, de Gasparo M Abstract After millennia of knowledge of opium, it was only recently that endogenous substances called opioids with similar properties to opium and derivatives were discovered. The first to be discovered were enkephalins. In addition to the regulation of their synthesis and expression of receptors, an important mechanism for the regulation of their functions carried out by multiple proteolytic enzymes acting at all levels of their structure is described. The action of such enzymes, known as enkephalinases, is also regulated by endogenous and exogenous factors which ultimately affect the con...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Ramírez-Sánchez M, Prieto I, Segarra AB, Martínez-Cañamero M, Banegas I, de Gasparo M Tags: Vitam Horm Source Type: research

Limbic circuit connectivity and the stress response: New insights into the mammalian nociceptin peptide system.
Abstract Considerable progress has been made in understanding the neurobehavioral effects of nociceptin peptide (N/OFQ) and its NOP receptor. Recent interest has focused on its role in stress and cognition, with consideration of therapeutic potential in regard to anxiety and mood disorders. Research has interrogated the mechanisms of action of N/OFQ peptide in the context of stress-related behavior. We are interested in the endogenous role of N/OFQ and NOP receptor in terms of adaptation to chronic stress. Our research has highlighted the importance of associated limbic regions including the bed nucleus, extended ...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Fulford AJ, Keskes S Tags: Vitam Horm Source Type: research

Enkephalins and ACTH in the mammalian nervous system.
ntilde;as R Abstract The pentapeptides methionine-enkephalin and leucine-enkephalin belong to the opioid family of peptides, and the non-opiate peptide adrenocorticotropin hormone (ACTH) to the melanocortin peptide family. Enkephalins/ACTH are derived from pro-enkephalin, pro-dynorphin or pro-opiomelanocortin precursors and, via opioid and melanocortin receptors, are responsible for many biological activities. Enkephalins exhibit the highest affinity for the δ receptor, followed by the μ and κ receptors, whereas ACTH binds to the five subtypes of melanocortin receptor, and is the only member of the ...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Duque-Díaz E, Alvarez-Ojeda O, Coveñas R Tags: Vitam Horm Source Type: research

Structure and dynamics of dynorphin peptide and its receptor.
lon A Abstract Dynorphin is a neuropeptide involved in pain, addiction and mood regulation. It exerts its activity by binding to the kappa opioid receptor (KOP) which belongs to the large family of G protein-coupled receptors. The dynorphin peptide was discovered in 1975, while its receptor was cloned in 1993. This review will describe: (a) the activities and physiological functions of dynorphin and its receptor, (b) early structure-activity relationship studies performed before cloning of the receptor (mostly pharmacological and biophysical studies of peptide analogues), (c) structure-activity relationship studie...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Ferré G, Czaplicki G, Demange P, Milon A Tags: Vitam Horm Source Type: research

Opioids and the hormone oxytocin.
Abstract The neuropeptide Oxytocin (ΟΤ) is involved as a neurohormone, a neurotransmitter, or a neuromodulator in an extensive range of central and peripheral effects, complex emotional and social human behaviors, memory and learning processes. It is implicated in homeostatic, neuroadaptive processes associated with stress responses and substance use via interactions with the hypothalamic-pituitary-adrenal (HPA) axis and the dopamine mesolimbic reward stress system. This chapter reviews the preclinical and clinical literature on the complicated relationships between endogenous and exogenous opioids and...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Kovatsi L, Nikolaou K Tags: Vitam Horm Source Type: research

Estrogens as arbiters of sex-specific and reproductive cycle-dependent opioid analgesic mechanisms.
Abstract The organization of estrogenic signaling in the CNS is exceedingly complex. It is comprised of peripherally and centrally synthesized estrogens, and a plethora of types of estrogen receptor that can localize to both the nucleus and the plasma membrane. Moreover, CNS estrogen receptors can exist independent of aromatase (aka estrogen synthase) as well as oligomerize with it, along with a host of other membrane signaling proteins. This ability of CNS estrogen receptors to either to physically pair or exist separately enables locally produced estrogens to act on multiple spatial levels, with a high degree of...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Gintzler AR, Storman EM, Liu NJ Tags: Vitam Horm Source Type: research

Opioids and reproduction.
t L Abstract More than 40years ago, the endogenous opioids were first described. Their role as important neuromodulators of pain and their influence on a variety of neuroendocrine control systems within the central nervous system has been recognized. More recently, endogenous opioids and their receptor have been identified in a variety of reproductive and non-reproductive tissues outside the central nervous system. What role the opioid system plays in these peripheral tissues and organs is not completely understood and thus the subjects of current research. In the central nervous system, endogenous opioids inhibit...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Seeber B, Böttcher B, D'Costa E, Wildt L Tags: Vitam Horm Source Type: research

Kappa opioid receptor and oligodendrocyte remyelination.
Abstract Adult oligodendrocyte precursor cells (OPCs) maintain the abilities to differentiate and myelinate denuded axons in demyelinating diseases, such as Multiple Sclerosis (MS), albert often inefficiently. Remyelination therapies seek to enhance endogenous remyelination and represent a promising approach to achieve functional and cellular architectural recovery against neuronal deficits. Recent findings indicate that the kappa opioid receptor (KOR), a G-protein coupled receptor (GPCR), plays an important role in regulating oligodendrocyte differentiation and myelination. In this chapter, we reviewed (1) curren...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Wang F, Mei F Tags: Vitam Horm Source Type: research

Inhibitory role of Gi-coupled receptors on cAMP-driven cancers with focus on opioid receptors in lung adenocarcinoma and its stem cells.
Abstract The development, progression, metastasis and drug resistance of the most common human cancers are driven by cyclic adenosine monophosphate (cAMP)-signaling downstream of beta-adrenergic receptors (β-Ars) coupled to the stimulatory G-protein Gs. Receptors coupled to the inhibitory G-protein Gi inhibit this signaling cascade by blocking the activation of the enzyme adenylyl cyclase that catalyzes the formation of cAMP and function as the physiological inhibitors of this signaling cascade. Members of the Gi-coupled receptor family widely expressed in the mammalian organism are GABA B receptors (GABAB-Rs...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Schuller HM Tags: Vitam Horm Source Type: research

Prenatal ethanol exposure and enkephalinergic neurotransmission.
K, Abate P Abstract Endogenous opioids (enkephalins, endorphins and dynorphins) are small peptides that play a main role in pain perception and analgesia, as well as in alcohol (ethanol) reinforcement and reward. Alcohol reinforcement involves the ethanol-induced activation of the endogenous opioid system, a process that may augment the hedonic value and the reinforcing properties of the drug, which in turn increases substance consumption. Changes in opioidergic transmission may contribute to alcohol intoxication and to the neuroadaptive responses produced by the long-lasting exposure to ethanol. Opioidergic tran...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Méndez M, Hernández-Fonseca K, Abate P Tags: Vitam Horm Source Type: research

Molecular aspects of delta opioid receptors.
yro G Abstract The delta opioid receptor (DOP) belongs to the Class A, rhodopsin-like family of G protein-coupled receptors. Although this receptor has a high level of similarity with the other opioid receptors, it displays unique aspects and functions. Indeed, as opposed to most membrane receptors, DOP is poorly addressed to the plasma membrane. In this chapter, we first review the molecular and cellular mechanisms regulating the expression and the cellular trafficking/sorting of DOP. We then summarize the structural insights of this receptor through the analysis of the existing crystal structures, with a particu...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Gendron L, Nagi K, Zeghal M, Giguère PM, Pineyro G Tags: Vitam Horm Source Type: research

The role of heat shock protein 90 in regulating pain, opioid signaling, and opioid antinociception.
Abstract Heat shock protein 90 (Hsp90) is one of the central signal transduction regulators of the cell. Via client interactions with hundreds of proteins, including receptors, receptor regulatory kinases, and downstream signaling regulators, Hsp90 has a crucial and wide-ranging impact on signaling in response to numerous drugs with impacts on resultant physiology and behavior. Despite this importance, however, Hsp90 has barely been studied in the context of pain and the opioid receptor system, leaving open the possibility that Hsp90 could be manipulated to improve pain therapeutic outcomes, a current area of mass...
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Streicher JM Tags: Vitam Horm Source Type: research

Preface.
PMID: 31421709 [PubMed - in process] (Source: Vitamins and Hormones)
Source: Vitamins and Hormones - August 20, 2019 Category: Endocrinology Authors: Litwack G Tags: Vitam Horm Source Type: research

Hepcidin cDNA evolution in vertebrates.
Abstract Hepcidin, belonging to the β-defensin family, was isolated for the first time from plasma and human urine. It is a cationic peptide, rich in cysteine bound with four disulfide bridges, which plays a major role in innate immunity and iron homeostasis. Some vertebrate species have multiple hepcidin homolog genes and each contains only one copy that functions as an iron regulator except hepcidin sequences in the pigeon (Columba livia). The aim of this chapter is to investigate the molecular evolution of several hepcidin gene from searches of the literature and public genomic databases from 17 different ...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Boumaiza M, Abidi S Tags: Vitam Horm Source Type: research

Regulators of hepcidin expression.
Abstract Iron, an essential nutrient, is required for many biological processes but is also toxic in excess. The lack of a mechanism to excrete excess iron makes it crucial for the body to regulate the amount of iron absorbed from the diet. This regulation is mediated by the hepatic hormone hepcidin. Hepcidin also controls iron release from macrophages that recycle iron and from hepatocytes that store iron. Hepcidin binds to the only known iron export protein, ferroportin, inducing its internalization and degradation and thus limiting the amount of iron released into the plasma. Important regulators of hepcidin, a...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Roth MP, Meynard D, Coppin H Tags: Vitam Horm Source Type: research

Splicing variant of hepcidin mRNA.
In this study, we firstly revealed that a new alternative HAMP transcript was found in hepatoma-derived cell line HLF, which was identical to the wild-type preprohepcidin sequence except lacking of an internal 60 bases. In addition to HLF, most of hepatoma-derived cell lines have significant copy numbers of variant-type hepcidin mRNA by a copy-based-digital PCR. Furthermore, the copy number of hepcidin mRNA variant was significantly higher in serum exosomes of hepatocellular carcinoma patients. The quantification of exosomal hepcidin mRNA variant may serve as a potential new biomarker for HCC diagnosis. PMID: 30798808...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Sasaki K, Kohgo Y, Ohtake T Tags: Vitam Horm Source Type: research

Hepcidin and IL-1 β.
Hepcidin and IL-1β. Vitam Horm. 2019;110:143-156 Authors: Kanamori Y, Murakami M, Sugiyama M, Hashimoto O, Matsui T, Funaba M Abstract Hepcidin expression is determined through transcriptional regulation by systemic iron status. However, acute or chronic inflammation also increases the expression of hepcidin, which is associated with the dysregulation of iron metabolism in pathological conditions. Interleukin (IL)-6 has been suggested to be a principal molecule to confer inflammation-related hepcidin transcription, which is mediated via signal transducer and activator of transcription (STAT)-bind...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Kanamori Y, Murakami M, Sugiyama M, Hashimoto O, Matsui T, Funaba M Tags: Vitam Horm Source Type: research

The role of heparin, heparanase and heparan sulfates in hepcidin regulation.
Abstract Hepcidin is considered the major regulator of systemic iron homeostasis in human and mice, and its expression in the liver is mainly regulated at a transcriptional level. Central to its regulation are the bone morphogenetic proteins, particularly BMP6, that are heparin binding proteins. Heparin was found to inhibit hepcidin expression and BMP6 activity in hepatic cell lines and in mice, suggesting that endogenous heparan sulfates are involved in the pathway of hepcidin expression. This was confirmed by the study of cells and mice overexpressing heparanase, the enzyme that hydrolyzes heparan sulfates, and ...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Asperti M, Denardo A, Gryzik M, Arosio P, Poli M Tags: Vitam Horm Source Type: research

Hepcidin-ferroportin axis in health and disease.
Abstract Hepcidin is central to regulation of iron metabolism. Its effect on a cellular level involves binding ferroportin, the main iron export protein, resulting in its internalization and degradation and leading to iron sequestration within ferroportin-expressing cells. Aberrantly increased hepcidin leads to systemic iron deficiency and/or iron restricted erythropoiesis. Furthermore, insufficiently elevated hepcidin occurs in multiple diseases associated with iron overload. Abnormal iron metabolism as a consequence of hepcidin dysregulation is an underlying factor resulting in pathophysiology of multiple diseas...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Ginzburg YZ Tags: Vitam Horm Source Type: research

Cardiomyocyte hepcidin: From intracellular iron homeostasis to physiological function.
Abstract Cellular iron is required for the utilization of oxygen in the cell. Iron in iron-sulfur and heme groups is required for electron transfer and oxygen activation in oxidative phosphorylation, while labile free iron is required for oxygen activation by dioxygenases, and as a catalyst for redox signaling. At the same time, this reactivity with oxygen underpins the production of cell-damaging free radicals in the presence of excess iron. Because the cardiac cell is a major site of oxygen flux, it requires tight control of intracellular iron levels. Until recently, such control was thought to be mediated predo...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Lakhal-Littleton S Tags: Vitam Horm Source Type: research

Hemochromatosis: Hereditary hemochromatosis and HFE gene.
Abstract Hereditary Hemochromatosis (HH) is an autosomal recessive genetic disease, characterized by an excessively increased absorption of dietary iron. Excess iron can be accumulated because of the lack of an effective excretory mechanism leading to toxic effects. HH is one of the most common genetic disorders in individuals of European descent. Genetic polymorphisms of the HFE gene (rs1800562, rs1799945 and rs1800730) also affect the normal activity of another protein, hepcidin, a negative regulator of iron homeostasis. If left untreated, hereditary hemochromatosis can lead to morbidity and eventually death. Cl...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Katsarou MS, Papasavva M, Latsi R, Drakoulis N Tags: Vitam Horm Source Type: research

Hepcidin, iron, and bacterial infection.
Abstract Hepcidin, an oligopeptide, has two major functions in mammals. Hepcidin regulates iron homeostasis by controlling iron export from absorptive enterocytes, hepatocytes, and macrophages into the circulation via ferroportin inactivation. Hepcidin is also an innate antimicrobial agent that is induced by invasive bacteria, limits bacterial proliferation by reducing iron in plasma and extracellular fluids, and kills bacteria. Herein, we review hepcidin and hepcidin genes, iron acquisition by bacteria, hepcidin actions in mice infected with selected extracellular and intracellular bacteria, and reports of corres...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Barton JC, Acton RT Tags: Vitam Horm Source Type: research

Hepcidin in chronic kidney disease anemia.
Abstract Chronic kidney disease (CKD) is associated with several complications that worsen with progression of disease; anemia, disturbances in iron metabolism and inflammation are common features. Inflammatory response starts early, releasing pro-inflammatory cytokines, acute phase reactants and hepcidin. Hepcidin production is modulated by several factors, as hypoxia/anemia, erythropoietin and erythropoiesis products, transferrin saturation (TSAT) and liver iron levels, which are altered in CKD. Treatment of CKD anemia is based on pharmaceutical intervention, with erythropoietic stimulating agents and/or iron su...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Santos-Silva A, Ribeiro S, Reis F, Belo L Tags: Vitam Horm Source Type: research

Signaling pathways regulating hepcidin.
Abstract Since its discovery in 2001, there have been a number of important discoveries and findings that have increased our knowledge about the functioning of hepcidin. Hepcidin, the master iron regulator has been shown to be regulated by a number of physiological stimuli and their associated signaling pathways. This chapter will summarize our current understanding of how these physiological stimuli and downstream signaling molecules are involved in hepcidin modulation and ultimately contribute to the regulation of systemic or local iron homeostasis. The signaling pathways and molecules described here have been s...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Rishi G, Subramaniam VN Tags: Vitam Horm Source Type: research

Hepcidin and the BMP-SMAD pathway: An unexpected liaison.
Abstract Hepcidin, the main regulator of iron metabolism, is synthesized and released by hepatocytes in response to increased body iron concentration and inflammation. Deregulation of hepcidin expression is a common feature of genetic and acquired iron disorders: in Hereditary Hemochromatosis (HH) and iron-loading anemias low hepcidin causes iron overload, while in Iron Refractory Iron Deficiency Anemia (IRIDA) and anemia of inflammation (AI), high hepcidin levels induce iron-restricted erythropoiesis. Hepcidin expression in the liver is mainly controlled by the BMP-SMAD pathway, activated in a paracrine manner by...
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Silvestri L, Nai A, Dulja A, Pagani A Tags: Vitam Horm Source Type: research

Preface.
PMID: 30798818 [PubMed - in process] (Source: Vitamins and Hormones)
Source: Vitamins and Hormones - February 27, 2019 Category: Endocrinology Authors: Litwack G Tags: Vitam Horm Source Type: research

Aldosterone Research: 65 Years, and Counting.
Abstract Aldosterone was characterized as the major mineralocorticoid hormone 65 years ago, and since then its physiologic role in epidural electrolyte homeostasis the province of nephrologists. In epithelia it acts via the mineralocorticoid receptor (MR) to retain Na+ and excrete K+; MRs, however, are widely expressed in organs not known to be aldosterone target tissues. MRs are not merely "aldosterone receptors," as they have equivalently high affinity for the physiologic glucocorticoids, and for progesterone. In epithelia (plus in the blood vessel wall and in the nucleus tractus solitarius of the brai...
Source: Vitamins and Hormones - January 29, 2019 Category: Endocrinology Authors: Funder JW Tags: Vitam Horm Source Type: research

Aldosterone and Ion Channels.
Abstract Since its discovery, aldosterone and ion modulation have been entwined. While scientific investigations throughout the decades have emphasized aldosterone's connection to Na+, K+, and H+ homeostasis, more recent research has demonstrated a relationship between aldosterone and Mg2+, Ca2+, and Cl- homeostasis. The mechanisms connecting aldosterone to ion regulation frequently involve ion channels; the membrane localized proteins containing at least one aqueous pore for ion conduction. In order to precisely control intracellular or intraorganelle ion concentrations, ion channels have evolved highly specific ...
Source: Vitamins and Hormones - January 29, 2019 Category: Endocrinology Authors: Valinsky WC, Touyz RM, Shrier A Tags: Vitam Horm Source Type: research

Non-Genomic Effects of Aldosterone.
Abstract Encouraging changes in the steroid hormone receptor field from initially questioning the role of non-genomic actions of steroid hormones to acceptance of the concept that the acute, membrane-centric actions are linked and/or regulate the nuclear actions. The focus of this chapter is how the non-genomic effects are linked to the longer lasting, genomic actions of aldosterone. By non-genomic we refer to the rapid actions that occur within minutes do not require transcription or translation and occur in both classical MR target organs (kidney and colon) and non-epithelial tissues (blood vessels, heart, and a...
Source: Vitamins and Hormones - January 29, 2019 Category: Endocrinology Authors: Mihailidou AS, Tzakos AG, Ashton AW Tags: Vitam Horm Source Type: research

Mineralocorticoid Receptor Antagonists.
Abstract Two mineralocorticoid receptor antagonists, spironolactone and eplerenone, are currently approved by the FDA. Several non-steroid based ligands are in clinical trials for indications including heart failure, hypertension and diabetic kidney disease, and even more structurally distinct chemical series are reported in the literature with preclinical data from animal models. Design of new ligands that are both selective over the other oxosteroid receptors (GR, PR and AR) and possess properties compatible with oral dosing, despite the overall lipophilic binding pocket of MR, remains a challenge. High-throughp...
Source: Vitamins and Hormones - January 29, 2019 Category: Endocrinology Authors: Nordqvist A, Granberg KL Tags: Vitam Horm Source Type: research

Evolution of the Mineralocorticoid Receptor.
Abstract The mineralocorticoid receptor (MR) and its kin, the glucocorticoid receptor (GR) evolved from an ancestral corticoid receptor (CR) in a cyclostome (jawless fish) through gene duplication and divergence. Distinct MR and GR orthologs first appear in cartilaginous fishes, such as sharks, skates, rays and chimaeras. Although aldosterone, the main physiological mineralocorticoid in humans and other terrestrial vertebrates, is not synthesized by cyclostomes or cartilaginous fishes, cyclostome CR and cartilaginous fish MR and GR are activated by aldosterone. Aldosterone first appears in lungfish, lobe-finned fi...
Source: Vitamins and Hormones - January 29, 2019 Category: Endocrinology Authors: Baker ME, Katsu Y Tags: Vitam Horm Source Type: research

Adipocyte Mineralocorticoid Receptor.
Abstract Mineralocorticoid receptor (MR) has been recently identified in adipose tissue, where its excessive activation contributes to several metabolic derangements often observed in obesity and metabolic syndrome. Recent findings support the existence of a bidirectional cross-talk between adipose tissue and adrenal glands, contributing to obesity-related hyperaldosteronism and subsequent adipocyte MR excessive activation. In this regard, MR pharmacological blockade has led to prevention of weight gain and metabolic benefits in murine models of genetic or diet-induced obesity. However, there is still a lack of kn...
Source: Vitamins and Hormones - January 29, 2019 Category: Endocrinology Authors: Infante M, Armani A, Marzolla V, Fabbri A, Caprio M Tags: Vitam Horm Source Type: research

Inhibitors of Aldosterone Synthase.
Abstract The mineralocorticoid aldosterone is an important regulator of blood pressure and electrolyte balance. However, excess aldosterone can be deleterious as a driver of inflammation, vascular remodeling and tissue fibrosis associated with cardiometabolic diseases. Mineralocorticoid receptor antagonists (MRA) and renin-angiotensin-aldosterone system (RAAS) antagonists are current clinical therapies used to antagonize deleterious effects of aldosterone in patients. MRAs compete with aldosterone for binding at its cognate receptor thereby limiting its effect while RAS antagonists reduce aldosterone levels indire...
Source: Vitamins and Hormones - January 29, 2019 Category: Endocrinology Authors: Weldon SM, Brown NF Tags: Vitam Horm Source Type: research