Horm Metab Res 2005; 37(7): 408-413
DOI: 10.1055/s-2005-870229
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Changes in Placental Dipeptidyl Peptidase IV in Preeclampsia with Intrauterine Growth Restriction

M.  Nishikawa1 , A.  Itakura2 , M.  Ito3 , M.  Takeuchi1 , Y.  Sato1 , H.  Kajiyama1 , S.  Mizutani1 , F.  Kikkawa1
  • 1Department of Obstetrics and Genecology, Nagoya University Graduate School of Medicine, Japan
  • 2Maternal & Perinatal Care Center, Nagoya University Hospital, Showa-ku, Nagoya, Japan
  • 3Toyohashi Municipal Hospital Toyohashi, Aichi, Japan
Further Information

Publication History

Received 19 August 2004

Accepted after revision 24 February 2005

Publication Date:
21 July 2005 (online)

Abstract

The purpose of this study was to examine alterations in placental expression of dipeptidyl peptidase IV (DPPIV). The localization of DPPIV was compared in control and preeclamptic placentas. Enzyme activity, mRNA, and protein expression were also measured. In term placentas, DPPIV was expressed preferentially in the fetal vascular endothelial cells within stem villi and only weakly in the villous stromal cells. DPPIV activity in control placentas showed no remarkable changes throughout gestation. Levels of activity in samples from normotensive control cases and women having preeclampsia with or without intrauterine growth restriction were 11.8 ± 2.1, 13.4 ± 1.1, and 15.3 ± 0.62 pmol pNA/min/mg protein, respectively. The preeclamptic placentas with intrauterine growth restriction thus showed significantly higher levels of activity than the controls (p < 0.05). We propose that placental DPPIV influences fetal metabolism via the degradation of fetoplacental circulating bioactive peptides, including incretins, resulting in the regulation of fetal growth.

References

  • 1 Feller A C, Radzum H J, Heymann E, Haas H, Scholz W, Parwaresch M R. A monoclonal antibody detecting dipeptidyl-peptidase IV in human tissue.  Virchows Arch Pathol Anat. 1986;  409 263-273
  • 2 Mizutani S, Sumi S, Narita O, Tomoda Y. Purification and properties of human placental dipeptidyl peptidase IV.  Acta Obst Gynaec Jpn. 1985;  37 769-775
  • 3 Mentlein R, Gallwitz B, Schmidt W E. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1 (7 - 36) amide, peptide histidine methionine and is responsible for their degradation in human serum.  Eur J Biochem. 1993;  214 829-835
  • 4 Kajiyama H, Kikkawa F, Suzuki T, Shibata K, Ino K, Mizutani S. Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma.  Cancer Res. 2002;  62 2753-2757
  • 5 Mizokami Y, Kajiyama H, Shibata K, Ino K, Kikkawa F, Mizutani S. Stromal cell-derived factor-1alpha-induced cell proliferation and its possible regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma.  Int J Cancer.. 2004;  110 652-659
  • 6 Kieffer T J, McIntosh C H, Pederson R A. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV.  Endocrinology. 1995;  136 3585-3596
  • 7 Pauly R P, Rosche F, Wermann M, McIntosh C H, Pederson R A, Demuth H U. Investigation of glucose-dependent insulinotropic polypeptide-(1 - 42) and glucagon-like peptide-1-(7 - 36) degradation in vitro by dipeptidyl peptidase IV using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A novel kinetic approach.  J Biol Chem. 1996;  271 23 222-26 229
  • 8 Deacon C F, Johnsen A H, Holst J J. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo.  J Clin Endocr Metab. 1995;  80 952-957
  • 9 Conarello S L, Li Z, Ronan J, Roy R S, Zhu L, Jiang G, Liu F, Woods J, Zycband E, Moller D E, Thornberry N A, Zhang B B. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci.  USA. 2003;  100 6825-6830
  • 10 Pederson R A, White H A, Schlenzig D, Pauly R P, McIntosh C H, Demuth H U. Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide.  Diabetes. 1998;  47 1253-1258
  • 11 Marguet D, Baggio L, Kobayashi T, Bernard A M, Pierres M, Nielsen P F, Ribel U, Watanabe T, Drucker D J, Wagtmann N. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26.  Proc Natl Acad Sci USA. 2000;  97 6874-6879
  • 12 Imai K, Kanzaki H, Fujiwara H, Maeda M, Ueda M, Suginami H, Mori T. Expression and localization of aminopeptidase N, neutral endopeptidase, and dipeptidyl peptidase IV in human placenta and fetal membranes.  Am J Obstet Gynecol. 1994;  170 1163-1168
  • 13 Sato Y, Fujiwara H, Higuchi T, Yoshioka S, Tatumi K, Maeda M, Fujii S. Involvement of dipeptidyl peptidase IV in extravillous trophoblast invasion and differentiation.  J Clin Endocr Metab. 2002;  87 4287-4296
  • 14 National High Blood Pressure Education Program Working Group . Report on high blood pressure in pregnancy.  Am J Obstet Gynecol. 2002;  183 S1-S22
  • 15 Zhu X D, Bonet B, Knopp R H. 17 β-estradiol, progesterone, and testosterone inversely modulate low-density lipoprotein oxidation and cytotoxicity in culture placental trophoblast and macrophges.  Am J Obstet Gynecol. 1997;  177 196-209
  • 16 Ito M, Itakura A, Ohno Y, Nomura M, Senga T, Nagasaka T, Mizutani S. Possible activation of the renin-angiotensin system in the feto-placental unit in pre-eclampsia.  J Clin Endocr Metab. 2002;  87 1871-1878
  • 17 Kliman H J, Nestler J E, Sermasi E, Sanger J M, Strauss JF III. Purification, characterization, and in Vitro differentiation of cytotrophoblasts from human term placentae.  Endocrinology. 1986;  118 1567-1582
  • 18 Misumi Y, Hayashi Y, Arakawa F, Ikehara Y. Molecular cloning and sequence analysis of human dipeptidyl peptidase IV, a serine proteinase on the cell surface.  Biochim Biophys Acta. 1992;  113 333-336
  • 19 Mizutani S, Okano K, Hasegawa E, Sakura H, Yamada M. Aminopeptidase A in human placenta.  Biochim Biophys Acta. 1981;  662 168-178
  • 20 Hariyama Y, Itakura A, Okamura M, Ito M, Murata Y, Nagasaka T, Nakazato H, Mizutani S. Placental aminopeptidase A as a possible barrier of angiotensin II between mother and fetus.  Placenta. 2000;  21 621-627
  • 21 Kikkawa F, Kajiyama H, Ino K, Watanabe Y, Ito M, Nomura S, Itakura A, Tsujimoto M, Mizutani S. Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (Gn-RH) in the dynamic pattern of placental hCG secretion via GnRH degradation.  Placenta. 2002;  23 483-489
  • 22 Johnson A R, Skidgel R A, Gafford J T, Erdos E G. Enzymes in placental microvilli: angiotensin I converting enzyme, angiotensinase A, carboxypeptidase, and neutral endopeptidase (“enkephalinase”).  Peptides. 1984;  5 789-796
  • 23 Avril I, Blondeau B, Duchene B, Czernichow P, Breant B. Decreased beta-cell proliferation impairs the adaptation to pregnancy in rats malnourished during perinatal life.  J Endocr. 2002;  174 215-223
  • 24 Bajoria R, Sooranna S R, Ward S, Hancock M. Placenta as a link between amino acids, insulin-IGF axis, and low birth weight: evidence from twin studies.  J Clin Endocr Metab. 2002;  87 308-315
  • 25 Unger R H, Eisentraut A M. The entero-insular axis.  Arch Intern Med. 1969;  123 261-266

A. Itakura

Maternal & Perinatal Care Center, Nagoya University Hospital

Showa-ku · Nagoya · Japan ·

Phone: +81 (52) 744 22 61

Fax: +81 (52) 744 22 68

Email: aita@med.nagoya-u.ac.jp

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