DOCSLIB.ORG

Evolution and Function of the Uterine Serpins (SERPINA14) Maria B

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Evolution and Function of the Uterine Serpins (SERPINA14) Maria B REVIEW ARTICLE Evolution and Function of the Uterine Serpins (SERPINA14) Maria B. Padua1, Peter J. Hansen2 1Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, FL, USA; 2Department of Animal Sciences, University of Florida, Gainesville, FL, USA Keywords Uterine serpins (recently designated as SERPINA14) are hormonally Immunoregulation, pregnancy, progesterone, induced proteins secreted in large quantities by the endometrial epithe- uterine milk proteins, uterine serpin lium during pregnancy. The SERPINA14 proteins belong to the serine proteinase inhibitor (serpin) superfamily, but their apparent lack of Correspondence Dr Maria B. Padua, PO Box 100294, inhibitory activity toward serine proteinases suggests that these proteins Department of Obstetrics and Gynecology, evolved a different function from the anti-proteinase activity typically University of Florida, Gainesville, found in most members of the serpin superfamily. The gene is present FL 32610-0294, USA. in a limited group of mammals in the Laurasiatheria superorder (rumi- E-mail: mpadua@ufl.edu nants, horses, pigs, dolphins and some carnivores) while being absent in primates, rodents, lagomorphs and marsupials. Thus, the gene is likely Submitted June 7, 2010; to have evolved by gene duplication after divergence of Laurasiatheria accepted June 8, 2010. and to play an important role in pregnancy. That role may vary between Citation species. In sheep, SERPINA14 probably serves an immunoregulatory role Padua MB, Hansen PJ. Evolution and function to prevent rejection of the fetal allograft. It is inhibitory to lymphocyte of the uterine serpins (SERPINA14). Am J proliferation and natural killer cell function. In the pig, SERPINA14 is Reprod Immunol 2010; 64: 265–274 involved in iron transport to the fetus by binding to and stabilizing the iron-binding protein uteroferrin. It is possible that SERPINA14 has doi:10.1111/j.1600-0897.2010.00901.x undergone divergence in function since the original emergence of the gene in a common ancestor of species possessing SERPINA14. SERPINA14 may regulate immune function in the Introduction sheep and placental iron transport in the pig. Pregnancy in mammals has evolved as a process that included the use of the existing genes for specific Nomenclature functions as well as the appearance of new genes formed by gene duplication that develop novel func- Uterine serpins were first described as progesterone- tions by sequence divergence from the parental induced proteins in the uterine fluid of the pregnant gene.1 Among the proteins involved in pregnancy of sheep (Ovis aries), pig (Sus scrofa) and cow (Bos tau- a limited group of mammals are the uterine serpins rus).2–4 The protein in sheep, discovered first, was (SERPINA14). During the course of evolution, SERP- called uterine milk protein (UTMP) because it was INA14 has been modified to exhibit high expression the major protein in uterine fluid (called uterine in the uterus under the regulation of progesterone. milk by Aristotle). The two uterine serpins found in In addition, unlike most of the members of the ser- the pig were originally known as uteroferrin-associ- ine proteinase inhibitor (serpin) superfamily, SERP- ated protein or uteroferrin-associated basic proteins INA14 has not retained the anti-proteolytic activity. (UfAP ⁄ UABP) because they form non-covalently Instead, SERPINA14 might have experienced con- heterodimers with uteroferrin.3,5 The homology tinue divergence since its formation so that the func- between the sequence of the sheep UTMP and some tion of the proteins may be species specific. Thus, members of the serpin superfamily was first found American Journal of Reproductive Immunology 64 (2010) 265–274 ª 2010 John Wiley & Sons A/S 265 PADUA AND HANSEN by Ing and Roberts.6 Later, Malathy et al.7 and was proposed that old designations be eliminated Mathialagan and Hansen8 found that the pig and proteins termed as uterine serpins (US). and cow proteins were similar to the sheep protein Recently, serpin genes have been categorized and also related to the serpin family. Afterward, it according to their phylogenetic relationship into 16 (a) Fig. 1 Phylogeny of SERPINA14. (a) Identifica- tion of species where SERPINA14 has been found in relationship to the types of placenta- tion. Orders with epitheliochorial placentation are represented by green branches whereas orders with either endotheliochorial or hemo- chorial type of placentation are in orange. Unresolved situations are shown by yellow branches. The superorders of eutherian mam- mals (Laurasiatheria, Euarchontoglires, Xenar- thra and Afrotheria) are shown on the illustration with the Marsupialia order as the outgroup of the tree. The presence of the SERPINA14 gene within Laurasiatheria is indi- cated by the blue check symbols whereas the red X symbols represent orders where the SERPINA14 gene was not identified after BLAST search of complete genomic sequences. The phylogenetic tree is modified from Vogel16, and the figure was reproduced from Padua et al.11 with permission from the FASEB Journal. (b) Phylogenetic tree of the SERPINA14 proteins inferred by the Neighbor- Joining method17 of the MEGA4 software.18 (b) The evolutionary distances were computed using the JTT matrix-based method19 where the rate of variation among sites was mod- eled with a gamma distribution (shape param- eter = 1.99) estimated from the data using the TREE_PUZZLE software.20,21 All positions con- taining gaps and missing data were eliminated from the dataset (Complete deletion option). The bootstrap test (1000 replicates) assessed the reliability of the branches in the phyloge- netic tree.22 The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. American Journal of Reproductive Immunology 64 (2010) 265–274 266 ª 2010 John Wiley & Sons A/S EVOLUTION AND FUNCTION OF SERPINA14 clades or classes (A–P). The largest clades in the clas- cluster and ovine and caprine forming another. Also, sification are Clade A and B which consists of extra- as expected, given the common ancestor between cellular or antitrypsin-like serpins and intracellular cetaceans and ruminants,24 the dolphin-like protein or ov-like serpins, respectively.9 All US that have was in a separate branch, but closer to the rumi- been described so far possess a 25-amino acid signal nants than to other species. The porcine SERPINA14 peptide sequence and are secreted into the uterine is more closely related to ruminants than to other lumen.8,10,11 Depending upon the analysis, phyloge- serpins and the equine, canine and panda bear-like netic studies have classified US as a highly divergent SERPINA14 proteins cluster together, with the two group of Clade A or as a separate clade.9,12,13 Upon carnivore species forming a sister clade. Note that discussion with James Whisstock and Gary Silver- while it was originally reported that there were two man, we asked the Human Genome Organization to SERPINA14 genes in the pig,8 only one gene was reserve the subclade 14 designation for US and this identified in the porcine genome.11 was agreed to. Since that time, US have been referred to as SERPINA14 in print.11,14,15 Structural and Enzyme-inhibitory Properties of SERPINA14 Evolution and Phylogeny of SERPINA14 The key region for serpins that inhibit proteinases is The SERPINA14 gene was first found in species with the reactive center loop (RCL), which is a flexible epitheliochorial placenta of the Ruminantia and Sui- structure localized on the top of the serpin and con- dae orders of the Laurasiatheria superorder of euthe- tains a complementary sequence to the active site of rian mammals.2–4 It is now known that, while still the target proteinase. The RCL is usually formed by somewhat limited in distribution among mammals, 20–25 amino acids and includes the hinge region at the SERPINA14 gene is present in a variety of other P15–P9 (with P1–P1¢ representing the scissile mammalian species (Fig. 1a) including those with bond).9,25,26 The hinge region provides mobility to epitheliochorial placenta [goat (Capra hircus) and the RCL, and there is a consensus pattern present in water buffalo (Bubalus bubalis) and dolphin (Tursiops the sequence for inhibitory serpins. Glycine is usu- truncatus – based on genomic information) in Cetar- ally present in the P15 position, threonine or serine tiodactyla and horse (Equus caballus) in Perissodac- is present at P14 position and acid residues with tyla] as well as one species of Carnivora with short side chains such as alanine, glycine or serine endotheliochorial placentation, the dog (Canis lupus are abundant in positions P12–P9.9 Analysis of the familiaris).11 Based on sequence identity in genomic hinge regions of all SERPINA14 proteins indicates DNA, original data presented in this paper are indic- that these serpins are not conserved with inhibitory ative that another carnivore, the panda bear (Ailuro- serpins and are probably not functional proteinase poda melanoleuca), also contains a SERPINA14 gene inhibitors.11 (Fig. 2). In addition to the lack of conservation of key There is also a non-functional SERPINA14 in a amino acid residues necessary for proteinase inhibi- third carnivore, the cat (Felis catus).11 Thus, it may tory activity, there is little biochemical evidence to be that not every carnivore expresses a functional indicate that the SERPINA14 proteins are non- SERPINA14 gene. In addition, the SERPINA14 gene is functional proteinase inhibitors. Ovine SERPINA14 not present in the Rodentia, Lagomorpha and An- had non-inhibitory activity against trypsin, chymo- thropoidea orders of the Euarchontoglires superorder trypsin, plasmin, thrombin, elastase, plasminogen nor in Marsupialia.11 These results suggest that the activator, cathepsins B, D or E, or dipeptidyl protein- SERPINA14 gene evolved only within the Laurasia- ase IV.6,8,27 Similarly, porcine SERPINA14 did not theria superorder of mammals, probably by gene inhibit trypsin or chymotrypsin.7 duplication from another serpin gene.
Load more

Recommended publications
  • Regulation of Lymphocyte Proliferation by Uterine Serpin: Interleukin-2 Mrna Production, CD25 Expression and Responsiveness to Interleukin-2 (44465) 2 1 MORGAN R
    Regulation of Lymphocyte Proliferation by Uterine Serpin: Interleukin-2 mRNA Production, CD25 Expression and Responsiveness to Interleukin-2 (44465) 2 1 MORGAN R. PELTIER,WEN-JUN LIU, AND PETER J. HANSEN Department of Dairy and Poultry Sciences, University of Florida, Gainesville, Florida 32611–0920 Abstract. During pregnancy, the endometrium of the ewe secretes large amounts of a progesterone-induced protein of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS). This protein inhibits lymphocyte proliferation in response to concanavalin A (ConA), phytohemagglutinin (PHA), or mixed lymphocyte reaction. The purpose of these experiments was to characterize the mechanism by which OvUS inhibits lymphocyte proliferation. Ovine US caused dose-dependent in- hibition of lymphocyte proliferation induced by phorbol myristol acetate (PMA), an activator of protein kinase C. The PHA-induced increase in CD25 expression was inhibited in peripheral blood mononuclear leukocytes (PBML) by OvUS. However, no effect of OvUS on Con A-induced expression of CD25 was observed. Further analysis using two-color flow cytometry revealed that OvUS inhibited ConA-induced expres- sion of CD25 in ␥␦-TCR− cells but not ␥␦-TCR+ cells. Stimulation of PBML for 14 hr with ConA resulted in an increase in steady state amounts of interleukin-2 (IL-2) mRNA that was not inhibited by OvUS. Ovine US was also inhibitory to lymphocyte proliferation induced by human IL-2. Results suggest that OvUS acts to inhibit lymphocyte prolif- eration by blocking the upregulation of the IL-2 receptor and inhibiting IL-2–mediated events. Lack of an effect of OvUS on ConA-stimulated CD25 expression in ␥␦-TCR+ cells may reflect a different mechanism of activation of these cells or insensitivity to inhibition by OvUS.
    [Show full text]
  • TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl Für
    TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Physiologie Differential gene expression during pre-implantation pregnancy in bos taurus Andréa Hammerle-Fickinger Vollständiger Abdruck der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigte Dissertation. Vorsitzender: Univ.-Prof. Dr. U. M. Kulozik Prüfer der Dissertation: 1. Univ.-Prof. Dr. H. H. D. Meyer (schriftliche Beurteilung) 2. Priv.-Doz. Dr. K. Kramer 3. Univ.-Prof. Dr. M. W. Pfaffl Die Dissertation wurde am 20.02.2012 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 22.05.2012 angenommen. Table of Contents Table of Contents List of abbreviations .......................................................................................................... iv Zusammenfassung............................................................................................................. vi Abstract............................................................................................................................. viii 1 Introduction .................................................................................................................. 1 1.1 Bovine estrous cycle .................................................................................................. 1 1.2 Activation of the complement system during pregnancy............................................
    [Show full text]
  • A Dissertation Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy
    MATERNAL IMMUNE CHANGES DURING BOVINE PREGNANCY: A FOCUS ON THE ENDOMETRIAL MACROPHAGE By LILIAN DE JESUS OLIVEIRA A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2010 1 © 2010 Lilian de Jesus Oliveira 2 To my parents Luiz Manoel and Maria Aparecida de Jesus, my brother and sister, Rodolfo Manoel and Luciana de Jesus Oliveira, my boyfriend Robson Fortes Giglio, and my major advisor, Dr. Peter J. Hansen 3 ACKNOWLEDGMENTS I would like to express my heartfelt thanks in having Dr. Peter J. Hansen as my major advisor. His guidance, support and challenges throughout my PhD program have made me grow not only as scientist but also as a person. His enthusiasm, knowledge and intelligence inspired me every day during these years. He is more than an advisor; he is a very good friend that I am glad to have the opportunity to meet. I am going to miss our weekly meetings. Also, I would like to thank my committee members, Dr. Nasser Chegini, Dr. William Thatcher, Dr. Daniel Sharp and Dr. Ammon Peck, for their contributions and suggestions for improving my research projects and academic training. I am also grateful to Dr. Joel Yelich his continuous support and the opportunity to teach in his class. This experience was indispensable to my formation as a teacher; his passion for teaching is contagious. I would like to thank my current lab mates, Dr. Silvia Carambula, Sarah Fields, Barbara Loureiro, Luciano and Aline Bonilla, Justin Fear, and Jim Moss, as well as my old lab mates, Dr.
    [Show full text]
  • Biological Role of Conceptus Derived Factors During Early Pregnancy In
    Biological Role of Conceptus Derived Factors During Early Pregnancy in Ruminants A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY IN ANIMAL SCIENCES UNIVERSITY OF MISSOURI- COLUMBIA Division of Animal Science By KELSEY BROOKS Dr. Thomas Spencer, Dissertation Supervisor August 2016 The undersigned have examined the dissertation entitled, BIOLOGICAL ROLE OF CONCEPTUS DERIVED FACTORS DURING EARLY PREGNANCY IN RUMINANTS presented by Kelsey Brooks, a candidate for the degree of doctor of philosophy, and hereby certify that, in their opinion, it is worthy of acceptance. __________________________________ Chair, Dr. Thomas Spencer ___________________________________ Dr. Rodney Geisert ___________________________________ Dr. Randall Prather ___________________________________ Dr. Laura Schulz ACKNOWLEDGMENTS I would like to acknowledge all the students, faculty and staff at Washington State University and the University of Missouri for their help and support throughout my doctoral program. I am grateful for the opportunity to work with Dr. Thomas Spencer, and thank him for his input and guidance not only in planning experiments and completing projects but for helping me turn my love of science into a career in research. I would also like to acknowledge the members of my graduate committee at Washington State University for their help and input during the first 3 years of my studies. A special thanks to Dr. Jim Pru and Cindy Pru for providing unlimited entertainment, and the occasional missing reagent. Thank you to my committee members at the University of Missouri for adopting me late in my program and helping shape my future as an independent scientist. Thanks are also extended to members of the Prather lab and Wells lab for letting me in on the secrets of success using the CRISPR/Cas9 system.
    [Show full text]
  • Spatio-Specific Regulation of Endocrine-Responsive Gene Transcription by Periovulatory Endocrine Profiles in the Bovine Reproductive Tract
    CSIRO PUBLISHING Reproduction, Fertility and Development, 2016, 28, 1533–1544 http://dx.doi.org/10.1071/RD14178 Spatio-specific regulation of endocrine-responsive gene transcription by periovulatory endocrine profiles in the bovine reproductive tract Estela R. Arau´joA, Mariana SponchiadoA, Guilherme PugliesiA, Veerle Van HoeckA, Fernando S. MesquitaB, Claudia M. B. MembriveCand Mario BinelliA,D ADepartment of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sa˜o Paulo, Avenida Duque de Caxias Norte, 225, Pirassununga, SP, 13635-900, Brazil. BSchool of Veterinary Medicine, Federal University of Pampa, Rodovia BR 472, 592, Uruguaiana, RS, 97508-000, Brazil. CCollege of Animal Science, University of Sa˜o Paulo State ‘Ju´lio de Mesquita Filho’, DracenaRodovia Comandante Joa˜o Ribeiro de Barros, km 651, Dracena, SP, 17900-000, Brazil. DCorresponding author. Email: [email protected] Abstract. In cattle, pro-oestrous oestradiol and dioestrous progesterone concentrations modulate endometrial gene expression and fertility. The aim was to compare the effects of different periovulatory endocrine profiles on the expression of progesterone receptor (PGR), oestrogen receptor 2 (ESR2), oxytocin receptor (OXTR), member C4 of aldo–keto reductase family 1 (AKR1C4), lipoprotein lipase (LPL), solute carrier family 2, member 1 (SLC2A1) and serpin peptidase inhibitor, clade A member 14 (SERPINA14): (1) between uterine horns ipsi- and contralateral to the corpus luteum (CL), (2) between regions of the ipsilateral horn and (3) in the vagina. Endometrium and vagina tissue samples were collected from cows that ovulated a larger (large follicle-large CL, LF-LCL; n ¼ 6) or smaller follicle (small follicle-small CL, SF-SCL; n ¼ 6) 7 days after oestrus.
    [Show full text]
  • Molecular and Cellular Studies of Drosophila Neuroserpin Spn4a And
    Molecular and Cellular Studies of Drosophila Neuroserpin Spn4A and its Polymer-Forming Mutants by Christine Chieh-Lin Lai B.Sc. University of British Columbia, 2008 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Microbiology & Immunology) The University of British Columbia (Vancouver) August 2010 © Christine Chieh-Lin Lai, 2010 1 Abstract Serpins (Serine Protease Inhibitors) are expressed by most organisms and perform a variety of functions. Most serpins inhibit proteases by undergoing a unique conformational change. They are clinically relevant in two ways. First, introduction of single amino acid point mutations transforms the serpins’ labile conformations into pathogenic, inactive polymers causing “serpinopathies”. In particular, human neuroserpin is a brain-specific serpin that, when mutated, causes a debilitating early onset dementia through unknown cellular pathways. Second, serpins are currently under investigation as therapeutic inhibitors of proprotein convertases (PCs). PCs are associated with some bacterial and viral infections as well as cancer. However, no comprehensive investigation into the cellular effects of PC inhibitor expression in mammalian cells has been performed. This thesis details the use of the Drosophila serpin, Spn4A, to address the cellular pathways mediated by serpin polymers or PC inhibition. Spn4A is a neuron-specific, secretory pathway serpin that inhibits Drosophila or human PCs. We hypothesized that Spn4A mutants, encoding homologous disease-causing mutations in human neuroserpin, would form pathogenic polymers and represent an ideal candidate for generating a cell-based and transgenic Drosophila serpinopathy model. Further, we hypothesized that we could evaluate the cellular response to PC inhibition and polymer accumulation by transcriptome profiling of H4 human neuroglioma cells expressing Spn4A wild-type and mutants.
    [Show full text]
  • Pepsin-Inhibitory Activity of the Uterine Serpins
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 13653–13658, November 1996 Biochemistry Pepsin-inhibitory activity of the uterine serpins (uterine secretory activityyaspartic proteinase inhibitoryprogesterone-induced uterine proteinyendometrium–trophoblast interaction) NAGAPPAN MATHIALAGAN*† AND THOMAS R. HANSEN‡ *Department of Animal Sciences, University of Missouri, Columbia, MO 65211; and ‡Department of Animal Sciences, University of Wyoming, Laramie, WY 82071 Communicated by Michael Roberts, University of Missouri, Columbia, MO, September 19, 1996 (received for review June 20, 1996) ABSTRACT Among the major products secreted by the distinct (20). Therefore, it was of considerable interest that uteri of cattle, sheep, and pigs during pregnancy are glyco- both species should produce large quantities of structurally proteins with amino acid sequences that place them in the similar progesterone-inducible products during pregnancy. serpin (serine proteinase inhibitor) superfamily of proteins. Hence the studies on uterine serpins have been extended. The inferred amino acid sequences for bovine uterine serpin Herein we demonstrate that these uterine serpins interact with (boUS-1) and ovine uterine serpin (ovUS-1) exhibit about 72% members of the aspartic proteinase family rather than with sequence identity to each other but only about 50% and 56% serine proteinases. They provide another example of serpins identity, respectively, to two distinct porcine uterine serpins with crossover function. (poUS-1 and poUS-2). Despite these differences in primary Because various acronyms were used for these uterine structure, the uterine serpins possess well-conserved reactive serpins before their general relatedness was revealed by mo- center loop regions that contain several motifs present in the lecular cloning studies, it is proposed that the previous desig- propeptide regions of pepsinogens.
    [Show full text]
  • Corticosteroid-Binding Globulin (Cbg): Deficiencies and the Role
    CORTICOSTEROID-BINDING GLOBULIN (CBG): DEFICIENCIES AND THE ROLE OF CBG IN DISEASE PROCESSES by LESLEY ANN HILL B.Sc. University of Western Ontario, 2011 A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENT FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Reproductive and Developmental Sciences) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2017 © Lesley Ann Hill, 2017 Abstract Corticosteroid-binding globulin (CBG, SERPINA6) is a serine protease inhibitor family member produced by hepatocytes. Plasma CBG transports biologically active glucocorticoids, determines their bioavailability to target tissues and acts as an acute-phase negative protein with a role in the delivery of glucocorticoids to sites of inflammation. A few CBG-deficient individuals have been identified, yet the clinical significance of this remain unclear. In this thesis, I investigated 1) the biochemical consequences of naturally occurring single nucleotide polymorphisms in the SERPINA6 gene, 2) the role of human CBG during infections and acute inflammation and 3) CBG as a biomarker of inflammation in rats. A comprehensive analysis of functionally relevant naturally occurring SERPINA6 SNP revealed 11 CBG variants with abnormal production and/or function, diminished responses to proteolytic cleavage of the CBG reactive center loop (RCL) or altered recognition by monoclonal antibodies. In a genome-wide association study, plasma cortisol levels were most closely associated with SERPINA6 SNPs and plasma CBG-cortisol binding capacity. These studies indicate that human CBG variants need to be considered in clinical evaluations of patients with abnormal cortisol levels. In addition, I obtained evidence that discrepancies in CBG values obtained by the 9G12 ELISA compared to CBG binding capacity and 12G2 ELISA are likely due to differential N-glycosylation rather than proteolysis, as recently reported.
    [Show full text]
  • Understanding the Influence of Synchronization of Ovulation On
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 8-2018 Understanding the influence of synchronization of ovulation on steroid bioavailability and its association with the presence of Pseudomonas aeruginosa within the bovine reproductive tract Sierra Ashley Lockwood University of Tennessee, [email protected] Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Recommended Citation Lockwood, Sierra Ashley, "Understanding the influence of synchronization of ovulation on steroid bioavailability and its association with the presence of Pseudomonas aeruginosa within the bovine reproductive tract. " PhD diss., University of Tennessee, 2018. https://trace.tennessee.edu/utk_graddiss/5060 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Sierra Ashley Lockwood entitled "Understanding the influence of synchronization of ovulation on steroid bioavailability and its association with the presence of Pseudomonas aeruginosa within the bovine reproductive tract." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Animal Science. Henry G. Kattesh, Major Professor We have read this dissertation and recommend its acceptance: Peter D. Krawczel, Ky G. Pohler, Justin D. Rhinehart, Brynn H. Voy, Brian K.
    [Show full text]
  • Antiproliferative Actions of Ovine Uterine Serpin
    Copyright Ó Blackwell Munksgaard, 2005 AJRI 2005; 53: 136–143 American Journal of Reproductive Immunology Antiproliferative Actions of Ovine Uterine Serpin Tekin S¸, Padua MB, Brad AM, Hansen PJ. Antiproliferative actions S¸aban Tekin1,2, Maria B. Padua1, of ovine uterine serpin. AJRI 2005; 53:136–143 Ó Blackwell Amber M. Brad1, Peter J. Hansen1 Munksgaard, 2005 1Department of Animal Sciences, University of Florida, Gainesville, FL, USA; 2Department of Biology, University PROBLEM: Ovine uterine serpin (OvUS) is a member of the serine of Gaziosmanpas¸a, Tokat, Turkey proteinase inhibitor superfamily and is the major protein produced by luminal and glandular epithelium of the sheep endometrium during mid to late pregnancy. The protein does not have prototypical proteinase inhibitory activity but can inhibit a wide variety of lymphocyte functions such as mitogen-induced proliferation and natural killer cell cytotoxicity. METHOD OF STUDY: The antiproliferative actions of OvUS were studied. RESULTS: It was demonstrated that, in addition to inhibiting lymphocyte proliferation, OvUS inhibits growth of two tumor cell lines (D17 and PC-3). The protein also interrupts development of pre- implantation embryos. Inhibition of cell proliferation is not universal, however, as OvUS did not inhibit growth of two non-tumorigenic cell lines (MDBK and BEND). The mechanism of action of inhibitory Key words: Lymphocytes, pre-implantation embryos, effects of OvUS is not known although experiments with inhibitors of proliferation, uterine serpin protein kinase A indicate that the protein does not inhibit lymphocyte proliferation through this pathway. Moreover, the protein does not Address reprint requests to Peter J. Hansen, PO Box 110910, Department of Animal Sciences, University induce apoptosis.
    [Show full text]
  • Regulation of DNA Synthesis and the Cell Cycle in Human Prostate Cancer Cells and Lymphocytes by Ovine Uterine Serpin Maria B Padua and Peter J Hansen*
    BMC Cell Biology BioMed Central Research article Open Access Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin Maria B Padua and Peter J Hansen* Address: Department of Animal Sciences, University of Florida, Gainesville, FL 32611-0910, USA Email: Maria B Padua - [email protected]; Peter J Hansen* - [email protected] * Corresponding author Published: 24 January 2008 Received: 17 August 2007 Accepted: 24 January 2008 BMC Cell Biology 2008, 9:5 doi:10.1186/1471-2121-9-5 This article is available from: http://www.biomedcentral.com/1471-2121/9/5 © 2008 Padua and Hansen; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Uterine serpins are members of the serine proteinase inhibitor superfamily. Like some other serpins, these proteins do not appear to be functional proteinase inhibitors. The most studied member of the group, ovine uterine serpin (OvUS), inhibits proliferation of several cell types including activated lymphocytes, bovine preimplantation embryos, and cell lines for lymphoma, canine primary osteosarcoma and human prostate cancer (PC-3) cells. The goal for the present study was to evaluate the mechanism by which OvUS inhibits cell proliferation. In particular, it was tested whether inhibition of DNA synthesis in PC-3 cells involves cytotoxic actions of OvUS or the induction of apoptosis. The effect of OvUS in the production of the autocrine and angiogenic cytokine interleukin (IL)-8 by PC-3 cells was also determined.
    [Show full text]
  • RESEARCH ARTICLE Intrinsic Expression of Transcortin in Neural Cells of the Mouse Brain: a Histochemical and Molecular Study
    245 The Journal of Experimental Biology 216, 245-252 © 2013. Published by The Company of Biologists Ltd doi:10.1242/jeb.076893 RESEARCH ARTICLE Intrinsic expression of transcortin in neural cells of the mouse brain: a histochemical and molecular study Elena Sivukhina1, Jean-Christophe Helbling2,3, Amandine M. Minni2,3, H. Hendrik Schäfer1, Véronique Pallet2,3, Gustav F. Jirikowski1 and Marie-Pierre Moisan2,3,* 1Institute of Anatomy II, Friedrich-Schiller University, Jena University Hospital, Jena, Germany, 2INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France and 3Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France *Address for correspondence ([email protected]) SUMMARY Corticosteroid binding globulin (CBG, transcortin) has been shown to be expressed in the brain of rat and human species. In this study, we examined the CBG brain expression and cDNA structure in mice, comparing wild-type (Cbg+/+) and Cbg knockout mice (Cbg–/–, obtained by genetic disruption of the SerpinA6 alias Cbg gene). We used double immunofluorescence labeling with specific neuronal and glial markers to analyze the cellular localization of CBG in various regions of the mouse brain. In wild-type (Cbg+/+) mice, we found CBG immunoreactivity in neuronal perikarya of the magnocellular hypothalamic nuclei, amygdala, hippocampus, cerebral cortex, cerebellum and pituitary. A portion of glial cells (astrocytes, oligodendrocytes) contained CBG immunoreactivity, including some of the ependymal cells and choroid plexus cells. No CBG immunoreactivity was detected in Cbg–/– brain tissues. Using RT-PCR, we showed that the full-length Cbg mRNA is present in those regions, indicating an intrinsic expression of the steroid-binding globulin.
    [Show full text]