DOCSLIB.ORG

Binding Globulin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Binding Globulin Observations on the Nature of the Underlying Disorder and the Occurrence of Associated Plasma Transport Abnormalities in a Patient with an Idiopathic Increase in the Plasma Thyroxine- binding Globulin Sidney H. Ingbar, … , Christine Waterhouse, Paul Cushman J Clin Invest. 1964;43(12):2266-2271. https://doi.org/10.1172/JCI105100. Research Article Find the latest version: https://jci.me/105100/pdf Journal of Clinical Investigation Vol. 43, No. 12, 1964 Observations on the Nature of the Underlying Disorder and the Occurrence of Associated Plasma Transport Ab- normalities in a Patient with an Idiopathic Increase in the Plasma Thyroxine- binding Globulin* SIDNEY H. INGBAR, CHRISTINE WATERHOUSE, AND PAUL CUSHMAN t (From the Thorndike Memorial Laboratory, Second and Fourth [Harvard] Medical Services, Boston, City Hospital, and the Department of Medicine, Harvard Medical School, Boston, Mass., and the Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, N. Y.) Since its discovery in 1952, much has been sponse to pregnancy or to the administration of learned concerning the thyroxine (T4)-binding estrogenic hormones, studies of these three pro- globulin of human plasma (TBG) [cf. Reviews teins, as well as the iron-binding globulin (trans- (1, 2)]. Although its concentration in plasma ferrin), in the serum of this patient were conducted has not been directly measured and is presum- in the basal state and during administration ably very low, the capacity of TBG to bind T4 is of large doses of diethylstilbestrol. The re- readily measured and is normally about 20 ug sponses of TBG and transferrin to an anabolic per 100 ml of serum or plasma (1). Recently, steroid, norethandrolone, were also assessed. several patients have been described in whom the T4-binding capacity of TBG is either greatly in- Methods creased or decreased, apparently on a hereditary Case history. Patient F. H. (Strong Memorial Hos- basis (3-8). Physiological studies in such pa- pital no. 46-32-67), a 66-year-old white female, was first tients have contributed much to a formulation of seen in 1958 and complained at that time of episodes of the role of this protein in the peripheral metabo- giddiness and vertigo, anxiety, tachycardia, and diaphore- lism of T4 (3, 5, 7, 8). On the other hand, little sis of about six months' duration. Weight loss, heat of intolerance, tremor, and palpitations were denied. A has been done to elucidate either the cause the goiter had been noted 40 years earlier and had not protein abnormality itself or the presence of asso- changed in the interim. The patient denied having re- ciated abnormalities in other plasma transport ceived any iodine-containing or hormonal medication. proteins. Physical examination revealed the blood pressure to be The availability of a patient with an apparently 100/85, the pulse rate 88. The thyroid gland was dif- in fusely enlarged, apparently without thrill, bruit, or nod- idiopathic increase the T4-binding capacity of ules. There were no physical signs of hypermetabolism. TBG has made possible further studies of this Significant laboratory data included the following: disorder. Since ceruloplasmin [cf. Review (9)] BMR, + 12%,, + 3%o; thyroidal 24-hour I's' uptake, 20%, and the corticosteroid-binding globulin (trans- 22%; serum protein-bound iodine (PBI), 11.2, 11.6, 10.6, cortin) (10-14), like TBG (15-17), normally in- 9.2 ,ug per 100 ml. trial of methimazole crease in concentration or in re- In view of the increased PBI, a binding activity was initiated. At a dosage of 30 mg daily, symptoms ap- * Submitted for publication June 29, 1964; accepted parently cleared, but the PBI remained 9.0 and 9.2 /Ag per July 27, 1964. 100 ml after 8 months of treatment. When the dose of Supported in part by research grant no. AM-00267-10 methimazole was increased to 40 mg daily, clinical signs from the National Institute of Arthritis and Metabolic of myxedema appeared, and the PBI declined to 0.9 ,ug Diseases, Bethesda, Md., and in part by U. S. Public per 100 ml. Methimazole was discontinued, and several Health Service research grant no. FR 44-03 from the weeks later, in May of 1960, 5 mc of In was adminis- Division of Research Facilities and Resources, National tered. The patient was asymptomatic at this time and Institutes of Health, Bethesda, Md. has remained so subsequently, although her thyroid de- t Present address: St. Luke's Hospital, New York, creased in size. In March 1961, laboratory tests revealed: N. Y. BMR, -7%, -5%O; PBI, 10.7 /Ag per 100 ml; serum 2266 IDIOPATHIC INCREASE IN TBG 2267 butanol extractable iodine, 8.8 ,ug per 100 ml; 24-hour thyroidal I3' uptake, 38%, decreasing to 5% after 7 days of treatment with 3,5,3'-triiodothyronine, 100 ,ug daily. In June 1961, an increase in the binding activity of 'o _ 0 0 0000 TBG was considered as the possible cause of her ab- 4t4 0 O 00 0\ U) normal PBI. Electrophoretic studies of her serum re- vealed the T4-binding activity of TBG to be greatly in- I - in 00 r 04 tn 440 - 0 ,I.o04- ' creased. In view of the persistently normal values for u4 CN o - BMR and thyroidal I131 uptake, both before and after .0 I'31 therapy, and the normal thyroid suppression test, it oE 4) .% would appear likely that the patient's persistently in- 00 N o creased PBI was never due to thyrotoxicosis, but was, 1') instead, a consequence of increased hormonal binding in the plasma. =.4 In August 1962, the patient was admitted to the Strong Memorial Hospital to receive a 3-week course of diethylstilbestrol, 30 mg daily. The control cervical '0o 00 0 smear revealed no evidence of estrogenic effect. A pro- 0* _44- gressive effect was noted during treatment, however, Cd and was marked by the time diethylstilbestrol was dis- 0 0 u) m o 0u)Cu 00Cr continued. Withdrawal vaginal bleeding followed a 0o'.nn 13 (1 14f\ 0 44 0 few days thereafter. 0 The patient was readmitted in November 1962 to re- 0t 4 U4s cq 0 (7 It'O o oc ceive a 3-week course of norethandrolone, 50 mg daily. During the treatment period, serum glutamic-oxalacetic o44 4.) 0 transaminase values increased from 20 to 60 U. Serum 00 0 t 0000tt-00 000 .0 bilirubin upon completion of therapy was 1 mg per 100 ml. .0 0 Balance studies performed during and after the a .k ot-cl C14 + ,O -9c4 treatment period revealed that norethandrolone induced o Fs in Mc4000 en 00040t0 significant nitrogen retention. 4en enX 00 u CNmM ) 4N- 000X In July of 1963, the patient was readmitted for a 44*4 second course of diethylstilbestrol treatment in order to 0 ~o .0F tne\0 C1400 f'14 '.4.4'3' verify the previously observed findings with regard to ._ a . the effects of this agent on T4-binding and to assess its 00-00 Lnnin c Lnm(4C4n to0 000Lto c ._ 4o ) bO a effects on other plasma transport proteins. o44 .0 Procedure. ._50 Thyroxine-binding capacities of TBG and H H thyroxine-binding prealbumin (TBPA) in serum were 0>4 measured by methods described in detail earlier, em- 0.x ploying paper electrophoresis in Tris-maleate buffer, pH .00 8.6 (7). Concomitantly, the distribution of tracer quan- 0 .04- t4 ''.3' "200'U- tities of P`31-labeled thyroxine, reflecting the binding of D>4c0 4 the endogenous hormone, was also assessed. Analyses 0 for the proportion of unbound T4 in serum were carried 0 3N _ )CZ 4 -00 00044 out by an equilibrium dialysis technique, recently de- 000 0 scribed in abstract form (18), to be described in detail la0 in a later communication. Serum PBI was measured by '.3 e 204e '2 b b4c 00' b440 IC nSo-oZ0.4 ._ a modification of the method of Zak (19). Plasma .5 17-OH corticosteroids were analyzed by the method of -.4 . - Hu m Peterson, Karrer, and Guerra (20), and transcortin H .c concentrations by the method of Daughaday, Adler, 0_>4 Mariz, and Rasinski (14). Ceruloplasmin was meas- 4)0 0 0 ured by the method of Scheinberg and Morell (21). a11 Serum iron-binding were measured capacities by the .0 method of Peters, Biovanniello, Apt, and Ross (22). 0 Coo o to o 0o > 4 Results 50x x aO a 11 Results obtained are presented in Table I and Figure 1. In the basal state, the patient's PBI on 2268 S. H. INGBAR, C. WATERHOUSE, AND P. CUSHMAN *-- P81 (Ag//COOmL) (28.2 per 100 ml) were within normal limits, x-x TBG Binding COacity (,ug r7 //OOmL x /O -') /ug &- --& Free 74 (%ftofo/x /02) as was the concentration of ceruloplasmin (25.4 o-o Free T4 Iodine (gg//OOmL x /03) mg per 100 ml). Total serum iron-binding ca- DIETHYLSTILBESTROL NORETHANDROLONE was at the upper (30 mg/day) (50mg/day) pacity limit of the normal range 12 (356 and 404 ptg per 100 ml), although serum iron 'o0 was normal (152 and 142 ug per 100 ml). 0~ 0 Response to diethylstilbestrol. During two 8 separate 3-week trials of diethylstilbestrol, no sig- 61- x A nificant change in the PBI, in the proportion of 4 unbound T4, or in the concentration of free T4- or- Q iodine in the serum occurred. The T4-binding 2 - capacity of TBG showed little, if any, response I to estrogen administration. During the first trial, 0 1 2 3 0 2 3 WEEKS OF TREATMENT WEEKS OF TREATMENT the binding capacity was 52 ug per 100 ml in the FIG.
Load more

Recommended publications
  • Types of Acute Phase Reactants and Their Importance in Vaccination (Review)
    BIOMEDICAL REPORTS 12: 143-152, 2020 Types of acute phase reactants and their importance in vaccination (Review) RAFAAT H. KHALIL1 and NABIL AL-HUMADI2 1Department of Biology, College of Science and Technology, Florida Agricultural and Mechanical University, Tallahassee, FL 32307; 2Office of Vaccines, Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD 20993, USA Received May 10, 2019; Accepted November 25, 2019 DOI: 10.3892/br.2020.1276 Abstract. Vaccines are considered to be one of the most human and veterinary medicine. Proteins which are expressed cost-effective life-saving interventions in human history. in the acute phase are potential biomarkers for the diagnosis The body's inflammatory response to vaccines has both of inflammatory disease, for example, acute phase proteins desired effects (immune response), undesired effects [(acute (APPs) are indicators of successful organ transplantation phase reactions (APRs)] and trade‑offs. Trade‑offs are and can be used to predict the ameliorative effect of cancer more potent immune responses which may be potentially therapy (1,2). APPs are primarily synthesized in hepatocytes. difficult to separate from potent acute phase reactions. The acute phase response is a spontaneous reaction triggered Thus, studying acute phase proteins (APPs) during vaccina- by disrupted homeostasis resulting from environmental distur- tion may aid our understanding of APRs and homeostatic bances (3). Acute phase reactions (APRs) usually stabilize changes which can result from inflammatory responses. quickly, after recovering from a disruption to homeostasis Depending on the severity of the response in humans, these within a few days to weeks; however, APPs expression levels reactions can be classified as major, moderate or minor.
    [Show full text]
  • Isoelectric Focussing of Human Thyroxine Binding Globulin (Thyropexin) and Human Prealbumin (Transthyretin)
    Luckenbach et al.: Isoelectric focussing of thyropexin and transthyretin 387 Eur. J. Clin. Chem. Clin. Biochem. Vol. 30, 1992, pp. 387-390 © 1992 Walter de Gruyter & Co. Berlin · New York Isoelectric Focussing of Human Thyroxine Binding Globulin (Thyropexin) and Human Prealbumin (Transthyretin) By Christine Luckenbach^ R. Wahl2 and E. Kailee2 1 Institut fur Anthropologie und Humangenetik 2 Medizinische Klinik und Poliklinik, Abteilung IV Eberhard-Karls- Universität Tübingen (Received November 7, 1991/Aprü 22, 1992) Summary: Two batches of the highly purified thyroid hormone-binding plasma proteins, human thyropexin and transthyretin, which were prepared in gram quantities for use in animal experiments, were subjected to analysis by isoelectric focussing. Under these conditions, it was observed that human transthyretin was composed of two components. This was presumably due to the use of 8 mol/1 urea. The preparations of both human transthyretin and human thyropexin contained some products of decomposition which probably arose in the course of the purification processes and, in addition, possibly also contained some normal genetic variants of human thyropexin. In spite of the alterations, both protein preparations largely retained their thyroid hormone-binding capacity, which is essential for in vivo studies on the re-entry of thyroid hormones from the extravascular space into the circulation. For therapeutic use in thyrotoxicosis, human transthyretin seems to be preferable to human thyropexin. Introduction The main thyroid hormone-binding plasma proteins severe thyrotoxicosis in emergencies: The concentra- in humans are thyropexin (1) ("TGB", human thy- tion of both T4 and T3 in the plasma can be signifi- roxine binding inter-alpha globulin (2))1) and trans- cantly enhanced by i.v.
    [Show full text]
  • Differential Expressions of Plasma Proteins in Systemic Lupus
    Journal of Microbiology, Immunology and Infection (2019) 52, 816e826 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.e-jmii.com Original Article Differential expressions of plasma proteins in systemic lupus erythematosus patients identified by proteomic analysis Rashmi Madda a,1, Shih-Chang Lin a,b,c,1, Wei-Hsin Sun a,**, Shir-Ly Huang d,* a Department of Life Sciences, National Central University, Taiwan b Department of Medicine, College of Medicine, Fu-Jen Catholic University, Taiwan c Division of Rheumatology and Immunology, Cathay General Hospital, Taiwan d Institute of Microbiology and Immunology, National Yang-Ming University, Taiwan Received 27 September 2017; received in revised form 18 January 2018; accepted 21 February 2018 Available online 29 March 2018 KEYWORDS Abstract Introduction: Systemic lupus erythematosus (SLE) is a chronic and complex autoim- Systemic lupus mune disease with a wide range of clinical manifestations that affects multiple organs and tis- erythematosus; sues. Therefore the differential expression of proteins in the serum/plasma have potential Biomarkers; clinical applications when treating SLE. Plasma proteins; Methods: We have compared the plasma/serum protein expression patterns of nineteen active LC-ESI-MS/MS; SLE patients with those of twelve age-matched and gender-matched healthy controls by pro- Lupus: 2D-gel teomic analysis. To investigate the differentially expressed proteins among SLE and controls, a electrophoresis; 2-dimensional gel electrophoresis coupled with high-resolution liquid chromatography tandem Proteomic analysis mass spectrometry was performed. To further understand the molecular and biological func- tions of the identified proteins, PANTHER and Gene Ontology (GO) analyses were employed. Results: A total of 14 significantly expressed (p < 0.05, p < 0.01) proteins were identified, and of these nine were up-regulated and five down-regulated in the SLE patients.
    [Show full text]
  • Ceruloplasmin
    CERULOPLASMIN OSR6164 4 x 18 mL R1 4 x 5 mL R2 Intended Use System reagent for the quantitative determination of Ceruloplasmin (CER) in human serum on Beckman Coulter AU analyzers. Summary Ceruloplasmin is the primary copper containing protein in plasma. It is a late acute phase reactant synthesized by the liver. Acute phase reactant refers to proteins whose serum concentrations rise significantly during acute inflammation due to causes including surgery, myocardial infarction, infections and tumours. Ceruloplasmin’s main clinical importance is in the diagnosis of Wilson’s disease. Here plasma Ceruloplasmin concentration is reduced while dialyzable copper concentration is increased. Increased ceruloplasmin levels are particularly notable in diseases of the reticuloendothelial system such as Hodgkin’s disease as well as during pregnancy or the use of contraceptive pills. Low plasma levels of 1,2 ceruloplasmin are found in malnutrition, malabsorption, nephrosis and severe liver disease, particularly biliary cirrhosis. Methodology Immune complexes formed in solution scatter light in proportion to their size, shape and concentration. Turbidimeters measure the reduction of incident light due to reflection, absorption, or scatter. In the procedure, the measurement of the decrease in light transmitted (increase in absorbance) through particles suspended in solution as a result of complexes formed during the antigen-antibody reaction, is the basis of this assay. System Information For AU400/400e/480, AU600/640/640e/680 and AU2700/5400 Beckman Coulter Analyzers. Reagents Final concentration of reactive ingredients: Solution of Polymers in Phosphate Buffered Saline (pH 7.4 – 7.6) Rabbit anti-human Ceruloplasmin antiserum Also contains preservatives. Precautions 1. For in vitro diagnostic use.
    [Show full text]
  • Immune Proteins, Enzymes and Electrolytes in Human Peripheral Lymph W.L
    156 Lymphology 11 (1978) 156-164 Immune Proteins, Enzymes and Electrolytes in Human Peripheral Lymph W.L. Olszewski, A. Engeset Laboratory for Haematology and Lymphology, Norsk Hydro's Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway, and The Department of Surgical Research andTransplantology, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland Summary bility. To do this, a better knowledge of kinetics Values of various biochemical constituents ofleg of transport of protein and other plasma consti­ lymph in 27 normal men have been presented. Con­ tuents to the tissue space of normal humans centration of immunoglobulins, complement proteins, seems to be necessary. acute phase reactants, enzymes, electrolytes and oth· er small molecular weight substances were measured. In the present paper we summarize the results of our studies on concentration of various pro­ Lymph forms part of the interstitial fluid with teins, among them of immunoglobulins, com­ a chemical composition resembling that of plement, and acute phase reactants, as well as blood plasma. It seems to be almost identical enzymes and electrolytes in the leg prenodal with the mobile tissue fluid. The concentra­ lymph in 27 men, during normal daily activities tion of macromolecules in tissue fluid and and experiments increasing the capillary filtra­ lymph depends on the ultrastructure of blood tion rate. We also analyze factors which cause capillaries and physical forces govepting trans­ variations in the level of biochemical consti­ port of substances across the capillary wall, tuents of tissue fluid and lymph. mostly hydrostatic and osmotic pressure gradients. The capillary wall acts as a molecu­ Materials and methods lar filter restricting free flow of proteins from Studies were carried out on 27 healthy male blood to the tissue space.
    [Show full text]
  • Blood Coagulation and Haemostasis: a Review*
    BLOOD COAGULATION AND HAEMOSTASIS: A REVIEW* E. M. RODF_~QUE,M.D. AND J. E. WYNANDS, M.D., C.IVI.~ FnOM THE V~Y F_~aLY STUVmS of this subject, many controversies existed regard- ing the various factors and mechanisms involved in the dotting process. One simply has to review the current literature and note the complex, often variable terminology, and the differing opinions of several workers in this field to realize that many of the former controversies are still present. However, many facts have been firmly established. This review will deal primarily with these facts and will mention the disputed points only when they appear pertinent to a better under- standing of the problems of controlling haemorrhage. Various factors are involved in the haemostatic process; the established ones include (1) the extravascular tissues; (2) the vasculature itself, the size and type of vessel being important; (3) the number of functioning platelets, and (4) the plasma coagulation system,x,2 THE ErmAVASCtrLABTISSUES While the extravaseular tissues do not play a major role in the control of bleeding, yet "their integrity and/or the variations in the resistance they offer to escaping blood may determine the bleeding response of a particular part of the body after injury. The "black eye' is a well-known example."2 In other situations in which there is easy bruisability, as in the aged, in poor nutrition, in some women, and in disease states such as the Ehlers-Danlos syndrome, it is likely that poor extravascular support is a deciding or contributing factor. 2 THE V~CULATVBE Previous to the more advanced and tested knowledge of today, abnormal vascular function was implicated as the basic pathogenetic factor in a variety of bleeding disorders.
    [Show full text]
  • Ceruloplasmin and Hypoferremia: Studies in Burn and Non-Burn Trauma Patients
    Antioxidants 2015, 4, 153-169; doi:10.3390/antiox4010153 OPEN ACCESS antioxidants ISSN 2076-3921 www.mdpi.com/journal/antioxidants Article Ceruloplasmin and Hypoferremia: Studies in Burn and Non-Burn Trauma Patients Michael A. Dubick 1,*, Johnny L. Barr 1, Carl L. Keen 2 and James L. Atkins 3 1 U.S. Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA; E-Mail: [email protected] 2 Departments of Nutrition and Internal Medicine, University of California, Davis, CA 95616, USA; E-Mail: [email protected] 3 Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-210-539-3680. Academic Editor: Nikolai V. Gorbunov Received: 26 November 2014 / Accepted: 28 February 2015 / Published: 6 March 2015 Abstract: Objective: Normal iron handling appears to be disrupted in critically ill patients leading to hypoferremia that may contribute to systemic inflammation. Ceruloplasmin (Cp), an acute phase reactant protein that can convert ferrous iron to its less reactive ferric form facilitating binding to ferritin, has ferroxidase activity that is important to iron handling. Genetic absence of Cp decreases iron export resulting in iron accumulation in many organs. The objective of this study was to characterize iron metabolism and Cp activity in burn and non-burn trauma patients to determine if changes in Cp activity are a potential contributor to the observed hypoferremia. Material and Methods: Under Brooke Army Medical Center Institutional Review Board approved protocols, serum or plasma was collected from burn and non-burn trauma patients on admission to the ICU and at times up to 14 days and measured for indices of iron status, Cp protein and oxidase activity and cytokines.
    [Show full text]
  • Translational Control of Ceruloplasmin Gene Expression: Beyond the IRE
    MAZUMDER ET AL. Biol Res 39, 2006, 59-66 59 Biol Res 39: 59-66, 2006 BR Translational control of ceruloplasmin gene expression: Beyond the IRE BARSANJIT MAZUMDER1, PRABHA SAMPATH2 and PAUL L. FOX3 1Department of Biology, Cleveland State University, Cleveland, OH, 2Department of Pathology, University of Washington, Seattle, WA, USA, and 3Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA ABSTRACT Translational control is a common regulatory mechanism for the expression of iron-related proteins. For example, three enzymes involved in erythrocyte development are regulated by three different control mechanisms: globin synthesis is modulated by heme-regulated translational inhibitor; erythroid 5- aminolevulinate synthase translation is inhibited by binding of the iron regulatory protein to the iron response element in the 5’-untranslated region (UTR); and 15-lipoxygenase is regulated by specific proteins binding to the 3’-UTR. Ceruloplasmin (Cp) is a multi-functional, copper protein made primarily by the liver and by activated macrophages. Cp has important roles in iron homeostasis and in inflammation. Its role in iron metabolism was originally proposed because of its ferroxidase activity and because of its ability to stimulate iron loading into apo-transferrin and iron efflux from liver. We have shown that Cp mRNA is induced by interferon (IFN)-γ in U937 monocytic cells, but synthesis of Cp protein is halted by translational silencing. The silencing mechanism requires binding of a cytosolic inhibitor complex, IFN-Gamma-Activated Inhibitor of Translation (GAIT), to a specific GAIT element in the Cp 3’-UTR. Here, we describe our studies that define and characterize the GAIT element and elucidate the specific trans-acting proteins that bind the GAIT element.
    [Show full text]
  • Fragment of Human Ceruloplasmin (Protein Structure/Ferroxidase/Copper Binding/Genetic Polymorphism/Evolution) I
    Proc. Natl. Acad. Sci. USA Vol. 76, No. 4, pp. 1668-1672, April 1979 Biochemistry Complete amino acid sequence of a histidine-rich proteolytic fragment of human ceruloplasmin (protein structure/ferroxidase/copper binding/genetic polymorphism/evolution) I. BARRY KINGSTON*, BRIONY L. KINGSTONt, AND FRANK W. PUTNAMt Department of Biology, Indiana University, Bloomington, Indiana 47405 Contributed by Frank W. Putnam, January 22, 1979 ABSTRACT The complete amino acid sequence has been a chain of human ceruloplasmin studied by McCombs and determined for a fragment of human ceruloplasmin [ferroxidase; Bowman (6) and probably corresponds to the a subunit pro- iron(II)oxygen oxidoreductase, EC 1.16.3.1]. The fragment posed by Simons and Bearn (4) and the chain of (designated Cp F5) contains 159 amino acid residues and has light Freeman a molecular weight of 18,650; it lacks carbohydrate, is rich in and Daniel (5). histidine, and contains one free cysteine that may be part of a The relation of Cp F5 to the structure of the intact cerulo- copper-binding site. This fragment is present in most commer- plasmin chain has to be deduced from indirect observations cial preparations of ceruloplasmin, probably owing to proteo- because of the small amount of single-chain ceruloplasmin lytic degradation, but can also be obtained by limited cleavage available to us and the strong interaction of the fragments. From of single-chain ceruloplasmin with plasmin. Cp F5 probably is the kinetics of the proteolytic cleavage of intact ceruloplasmin an intact domain attached to the COOH-terminal end of sin- gle-chain ceruloplasmin via a labile interdomain peptide bond.
    [Show full text]
  • Investigating an Increase in Florida Manatee Mortalities Using a Proteomic Approach Rebecca Lazensky1,2, Cecilia Silva‑Sanchez3, Kevin J
    www.nature.com/scientificreports OPEN Investigating an increase in Florida manatee mortalities using a proteomic approach Rebecca Lazensky1,2, Cecilia Silva‑Sanchez3, Kevin J. Kroll1, Marjorie Chow3, Sixue Chen3,4, Katie Tripp5, Michael T. Walsh2* & Nancy D. Denslow1,6* Two large‑scale Florida manatee (Trichechus manatus latirostris) mortality episodes were reported on separate coasts of Florida in 2013. The east coast mortality episode was associated with an unknown etiology in the Indian River Lagoon (IRL). The west coast mortality episode was attributed to a persistent Karenia brevis algal bloom or ‘red tide’ centered in Southwest Florida. Manatees from the IRL also had signs of cold stress. To investigate these two mortality episodes, two proteomic experiments were performed, using two‑dimensional diference in gel electrophoresis (2D‑DIGE) and isobaric tags for relative and absolute quantifcation (iTRAQ) LC–MS/MS. Manatees from the IRL displayed increased levels of several proteins in their serum samples compared to controls, including kininogen‑1 isoform 1, alpha‑1‑microglobulin/bikunen precursor, histidine‑rich glycoprotein, properdin, and complement C4‑A isoform 1. In the red tide group, the following proteins were increased: ceruloplasmin, pyruvate kinase isozymes M1/M2 isoform 3, angiotensinogen, complement C4‑A isoform 1, and complement C3. These proteins are associated with acute‑phase response, amyloid formation and accumulation, copper and iron homeostasis, the complement cascade pathway, and other important cellular functions.
    [Show full text]
  • Ceruloplasmin, Transferrin and Apotransferrin Facilitate Iron Release from Human Liver Cells
    FEBS 18623 FEBS Letters 411 (1997) 93-96 Ceruloplasmin, transferrin and apotransferrin facilitate iron release from human liver cells Stephen P. Young*, Magdy Fahmy, Simon Golding1 Department of Rheumatology, University of Birmingham, Edghaston, Birmingham Bl5 2TT, UK Received 7 April 1997 for apotransferrin on these cells. In support of this role for Abstract The rate of iron release from HepG2 liver cells was increased not only by extracellular apotransferrin, but also by transferrin in iron release, Baker et al. showed that the release of iron from freshly isolated rat hepatocytes, labelled in vivo diferric transferrin, in a non-additive, concentration-dependent o9 manner and to a similar magnitude. This suggests that rapid with Fe, was accelerated by chelators, serum and apotrans- equilibration between receptor-mediated uptake and the release ferrin [4], although the transferrin effect was not observed by process determines net iron retention by the liver. Release was all workers [5]. also accelerated by ceruloplasmin; most importantly, the effect The oxidation state of the iron is a crucial factor in its of this protein was greatest when iron release was occurring mobilization. Iron is bound to transferrin in the ferric, iron rapidly, stimulated by apotransferrin, or under conditions of (III) state, yet most intracellular iron is released from ferritin, limited oxygen. Thus iron release involves both apotransferrin the primary intracellular iron storage protein, in the ferrous and ferrotransferrin, with ceruloplasmin playing a role in tissues with limited oxygen supply, as in the liver in vivo. iron (II) form. An oxidation step is therefore required before this iron may be effectively mobilized outside the cell.
    [Show full text]
  • Vitamin and Minerals and Neurologic Disease
    Vitamin and Minerals and Neurologic Disease Steven L. Lewis, MD World Congress of Neurology October 2019 Dubai, UAE [email protected] Disclosures . Dr. Lewis has received personal compensation from the American Academy of Neurology for serving as Editor-in-Chief of Continuum: Lifelong Learning in Neurology and for activities related to his role as a director of the American Board of Psychiatry and Neurology, and has received royalty payments from the publishers Wolters Kluwer and Wiley-Blackwell for book authorship. He has no disclosures related to the content or topic of this talk. Objective . Discuss the association of trace mineral deficiencies and vitamin deficiencies (and excess) with neuropathy and myeloneuropathy and other peripheral neurologic syndromes Outline of Presentation . List minerals relevant to neuropathy or myeloneuropathy . Proceed through each mineral and its associated clinical syndrome . List vitamins relevant to neuropathy or myeloneuropathy . Proceed through each vitamin and its associated clinical syndrome Minerals . Naturally occurring nonorganic homogeneous substances . Elements . Required for optimal metabolic and structural processes . Both cations and anions . Essential trace minerals: must be supplied in the diet . Some have recommended daily allowances (RDA) Macrominerals . Sodium . Potassium . Calcium . Magnesium . Phosphorus . Sulfur Macrominerals . Sodium . Potassium . Calcium . Magnesium . Phosphorus . Sulfur Trace Minerals . Chromium . Cobalt . Copper . Iodine . Iron . Manganese . Molybdenum . Selenium . Zinc Trace Minerals . Chromium . Cobalt . Copper . Iodine . Iron . Manganese . Molybdenum . Selenium . Zinc Generalized dose-reponse curve for an essential nutrient Howd and Fan, 2007 Copper . Essential trace element . Human body contains approximately 100 mg Cu . Cofactor of many redox enzymes . Ceruloplasmin most abundant of the cuproenzymes . Involved in antioxidant defense, neuropeptide and blood cell synthesis, and immune function1 1 Bost, J Trace Elements 2016 Copper Deficiency .
    [Show full text]