Advances in clinical chemistry vol 54

ADVANCES IN CLINICAL CHEMISTRY VOLUME 54 This page intentionally left blank Advances in CLINICAL CHEMISTRY Edited by GREGORY S MAKOWSKI Clinical Laboratory Partners Newington, CT Hartford Hospital Hartford, CT VOLUME 54 AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 32 Jamestown Road, London NW1 7BY, UK 225 Wyman Street, Waltham, MA 02451, USA 525 B Street, Suite 1900, San Diego, CA 92101-4495, USA Radarweg 29, PO Box 211, 1000 AE Amsterdam, The Netherlands This book is printed on acid-free paper ϱ Copyright ß 2011, Elsevier Inc All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333; email: permissions@elsevier.com Alternatively you can submit your request online by visiting the Elsevier web site at http://www.elsevier.com/locate/permissions, and selecting Obtaining permission to use Elsevier material Notice No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN: 978-0-12-387025-4 ISSN: 0065-2423 For information on all Academic Press publications visit our website at www.elsevierdirect.com Printed and bound in USA 11 12 13 14 10 CONTENTS CONTRIBUTORS ix PREFACE xi Heat-shock Proteins in Cardiovascular Disease JULIO MADRIGAL-MATUTE, JOSE LUIS MARTIN-VENTURA, LUIS MIGUEL BLANCO-COLIO, JESUS EGIDO, JEAN-BAPTISTE MICHEL, AND OLIVIER MEILHAC Abstract Introduction Atherogenesis and Possible Stimuli of Inducible HSPs HSPs/Anti-HSPs as Biomarkers of Atherothrombosis Molecular Mechanisms: Bystanders or Actors? HSP as Therapeutic Targets in CVD/Atherothrombosis Conclusions Acknowledgments References 3 15 25 28 28 29 Polyamines in Cancer EDWIN A PAZ, JENARO GARCIA-HUIDOBRO, AND NATALIA A IGNATENKO Abstract Introduction Overview of Polyamine Regulation Deregulation of Polyamines in Cancer Genetic Variability in ODC Affecting Carcinogenesis EIF5A and Cancer Chemoprevention Strategies Within Polyamine Pathway Acknowledgments References v 46 46 47 50 54 56 60 63 63 vi CONTENTS Acquired Hemophilia A MASSIMO FRANCHINI, AND GIUSEPPE LIPPI Abstract Introduction Pathogenesis Laboratory Diagnosis Conclusions Acknowledgments References 71 72 72 73 78 79 79 Hypobetalipoproteinemia: Genetics, Biochemistry, and Clinical Spectrum PATRIZIA TARUGI, AND MAURIZIO AVERNA 10 Abstract Introduction Pathways of apoB-Containing Lipoproteins Production Dominant Forms of Primary HBL Recessive Forms of Primary HBL Primary Orphan FHBL Spectrum of Clinical Manifestations in Primary HBL Main Clinical Issues of FHBL Secondary Hypobetalipoproteinemias Conclusions Addendum Acknowledgment References 82 83 83 87 91 92 92 94 96 97 99 101 101 Sm Peptides in Differentiation of Autoimmune Diseases MICHAEL MAHLER Abstract Introduction Systemic Lupus Erythematosus Mixed Connective Tissue Disease Biochemical Aspects of the Sm Antigen Characteristics of Anti-Sm Antibodies Detection of Anti-Sm Antibodies Clinical Association of Anti-Sm Antibodies 109 110 110 112 112 113 114 118 CONTENTS 10 11 12 13 Meta-Analysis of Anti-Sm Antibodies Genesis of Anti-Sm Antibodies (Sm) Peptides as Antigens Summary and Conclusion Take Home Messages References vii 118 119 119 122 122 122 Aromatase Activity and Bone Loss LUIGI GENNARI, DANIELA MERLOTTI, AND RANUCCIO NUTI Abstract Introduction Aromatase and Sources of Estrogen Production The Aromatase Gene and Its Tissue-Specific Regulation Aromatase Deficiency and the Bone Skeletal Consequences of Aromatase Excess Threshold Estradiol Hypothesis for Skeletal Sufficiency Variability in the Level of Aromatase Activity: Effects on Bone Metabolism Summary and Conclusions References 129 130 131 133 134 145 146 148 153 154 Biochemistry of Adolescent Idiopathic Scoliosis GIOVANNI LOMBARDI, MARIE-YVONNE AKOUME, ALESSANDRA COLOMBINI, ALAIN MOREAU, AND GIUSEPPE BANFI Abstract Introduction Bone Biochemical Parameters Hormones Trace Elements Hematological Parameters—Platelets Melatonin Conclusions References 166 166 168 168 171 171 172 178 179 INDEX 183 This page intentionally left blank CONTRIBUTORS Numbers in parentheses indicate the pages on which the authors’ contributions begin MARIE-YVONNE AKOUME (165), Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital Research Center; and Department of Biochemistry, Faculty of Medicine, Universite´ de Montre´al, Montre´al, Quebec, Canada MAURIZIO AVERNA (81), Department of Clinical Medicine and Emerging Diseases, University of Palermo, Palermo, Italy GIUSEPPE BANFI (165), IRCCS Istituto Ortopedico Galeazzi, Milano, Italy LUIS MIGUEL BLANCO-COLIO (1), Vascular Research Lab, IIS, Fundacio´n Jime´nez Dı´az, Auto´noma University, Av Reyes Cato´licos 2, Madrid, Spain ALESSANDRA COLOMBINI (165), IRCCS Istituto Ortopedico Galeazzi, Milano, Italy JESUS EGIDO (1), Vascular Research Lab, IIS, Fundacio´n Jime´nez Dı´az, Auto´noma University, Av Reyes Cato´licos 2, Madrid, Spain MASSIMO FRANCHINI (71), Department of Pathology and Laboratory Medicine, Immunohematology and Transfusion Center, University Hospital of Parma, Parma, Italy JENARO GARCIA-HUIDOBRO (45), Biochemistry and Molecular and Cellular Biology Graduate Program, University of Arizona, Tucson, Arizona, USA LUIGI GENNARI (129), Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy NATALIA A IGNATENKO (45), Department of Cell Biology and Anatomy, Arizona Cancer Center, Tucson, Arizona, USA ix BIOCHEMISTRY OF ADOLESCENT IDIOPATHIC SCOLIOSIS 175 7.3 INTERACTION WITH CALCIUM METABOLISM Melatonin biosynthesis is regulated by acetyltransferase expression and posttranslational control mechanisms via the changes in intracellular concentration of cAMP/calmodulin/Ca2ỵ following adrenergic stimulation [51] Calmodulin is also a melatonin-binding protein of considerable regulatory significance Its affinity to melatonin is sufficient for mediating effects at elevated physiological concentrations, and this binding is responsible for inhibition of calmodulin action In particular, this interaction is specific to calcium-activated calmodulin and results in the inhibition of the CaM (calmodulin) kinase II Moreover, melatonin binding to membrane receptors induces the activation of the bg complex of G proteins that stimulate PLCb and thus induces the activation of PKCa that in turn catalyzes production of phosphorylate calmodulin, perpetuating its inhibition These interactions are important in inducing cytoskeleton rearrangements [51,52] As reported above, calmodulin is a calcium-binding receptor protein that regulates cAMP-based enzyme systems, and thereby the contractile properties of muscle cells via cell membrane regulation of Ca2ỵ transport [53] As such, melatonin may modulate diurnally many cellular functions involving calcium transport [52] Melatonin modulates a specific cellular function through the kinetics of its binding to calmodulin [54] Since calmodulin and melatonin exert a reciprocal antagonism in various tissues, and probably on skeletal muscle as well, it is reasonable to assume that the melatonin and calmodulin interplay could contribute to modulating paraspinal muscle tone and activity in AIS [48] Because pineal deficiency modulates calcium-activated calmodulin, the spinal cord contractile proteins may be affected and neural cells may fail to grow in response to stretch In addition, scavengers may not satisfactorily ‘‘mop-up’’ free radicals produced by stretch, causing cellular damage and inadequate cord growth It has been proposed that asynchronous growth between the spinal cord and vertebrae (bone growth) could be part of the pathologic mechanism leading to scoliosis [55] It has been demonstrated that administration of calmodulin antagonists, such as tamoxifen and trifluoperozine, mimicks the inhibitory effects of melatonin and can stop progression of this disease in mice [53] Experiments conducted on bone-derived cell lines have proven that melatonin can increase expression of bone sialoprotein as well as several other essential bone marker proteins, including ALP, osteocalcin, and type I collagen Melatonin stimulated both osteoblast differentiation and mineralization In ovariectomized rats (a model of postmenopausal osteoporosis), 176 LOMBARDI ET AL the administration of physiologic melatonin doses with adequate estrogen or pharmacologic melatonin doses is required to increase bone mineral content and/or bone mineral density [56] 7.4 ROLE OF MELATONIN IN PATHOGENESIS OF SCOLIOSIS The role of melatonin in scoliosis was first identified by experiments in chickens Pinealectomy, performed in chickens shortly after they hatch, induced scoliosis [57–59] Chickens, as bipedal animals, developed spinal disease with anatomic features similar to human AIS It has been hypothesized that melatonin deficiency interferes with the normal symmetrical growth of the proprioceptive system involving the paraspinal muscles and the spine [60] An asymmetric expression in bilateral paravertebral muscles of melatonin receptor MT2 mRNA in scoliotic patients was actually demonstrated, but it may merely be a secondary effect caused by forces exerted on the abnormally curved spine [61] The administration of melatonin in pinealectomized chickens prevented scoliosis onset and development [60] The same group also reported a significant decrease of nocturnal serum melatonin concentration in adolescents characterized by progressive scoliosis, whereas in patients with a stable deformity the concentration was not significantly different from controls [54] Although experimental spinal disease was also reproduced in pinealectomized rats, it should be mentioned that scoliosis only developed in bipedal rats with surgically removed forelimbs and tails [62] Similar findings were reported in a strain of mice (C57BL/6) where the gene controlling the melatonin pathway is naturally knocked out [63] Melatonin deficiency secondary to pinealectomy alone does not produce scoliosis if the quadruped condition is maintained: the postural mechanism is thus crucial for inducing vertebral column abnormalities [1] Although low melatonin concentration in severe progressive human scoliosis was corroborated by experimental animal studies [54], additional studies did not unequivocally confirm melatonin deficiency in AIS For example, a study was performed using morning and evening urine samples collected from adolescent scoliotic females [64] This report showed no difference in melatonin concentration (measured by high pressure liquid chromatography) versus controls [64] Another study found that serum melatonin concentrations during the day (2 p.m.) and at night (2 a.m.) were not significantly different between a group of seven AIS patients and seven age-matched controls [14] The same authors also did not confirm the previously demonstrated melatonin preventive effect on scoliotic development in pinealectomized chickens In their experiments, the intraperitoneal injection of melatonin had no effect on scoliosis genesis or on disease progression [65] BIOCHEMISTRY OF ADOLESCENT IDIOPATHIC SCOLIOSIS 177 Melatonin is rapidly metabolized in the liver by hydroxylation The principal catabolite in urine is 6-sulfatoxymelatonin, whose concentration can reflect the serum melatonin levels The evaluation of its excretion in urine from AIS patients did not show differences during the entire 24-h collection period (or in diurnal and nocturnal collections) versus age- and gendermatched controls [66] Similar results were reported by another team that compared serum melatonin and urine 6-sulfatoxymelatonin [67] No differences in melatonin concentration were observed in homogenates of paravertebral muscles obtained from scoliotic and nonscoliotic adolescents or in comparison between sides (convex and concave) in AIS patients [46] It should be noted that absolute melatonin concentration may be less important than its secretion rhythm, a property that could greatly influence cell metabolism through receptor occupancy and regulation The role of melatonin in AIS remained uncertain due to the questionable relevance of avian studies versus humans These issues were compounded by experimental data obtained from primates For example, a 2-years study on 18 pinealectomized monkeys failed to induce scoliosis [68] Positron emission tomography (PET) was used to evaluate F-18 fluorodeoxyglucose metabolism in the pineal gland versus the cerebellar area No metabolic differences were found in AIS versus control subjects [69] Urine 6-sulfatoxymelatonin concentration was also similar in the two groups Biochemical and metabolic data did not support the hypothesis of absolute melatonin deficiency as a cause of AIS Increased incidence of AIS was not found in children after surgical or radio-therapeutic pinealectomy due to cancers, despite melatonin deficiency Interestingly, scoliotic patients typically suffer from sleep difficulty and disturbance Transient deficiencies of melatonin synthesis or perturbation in its signal transduction could explain the discrepancies found between these reports Administration of melatonin in AIS patients with a low concentration of endogenous melatonin was studied in a group of 40 subjects (28 with stable scoliosis and 12 with progressive scoliosis) Melatonin was measured by a radioimmunoassay from samples drawn every h for 24 h Environmental illumination was held constant from a.m to p.m Integrated melatonin concentration in 25 control subjects was 368 pg/mL (standard error 28.5) within a 24-h period: 183 (49.8) pg/mL for the nocturnal period (from midnight to a.m.) and 10 (2.5) pg/mL for daytime (from a.m to p.m.) The circadian rhythm was preserved in patients as well Twenty two patients had melatonin concentrations similar to those of controls whilst 18 patients had lower concentrations The administration of melatonin to patients did not alter the biologic rhythm, and prevented, in mild cases (curvature