ROLA AMINOPEPTYDAZ ŁOŻYSKOWYCH W PRZEBIEGU CIĄŻY
DOI:
https://doi.org/10.56782/pps.46Keywords:
placental proteases, placental aminopeptidases, gestational hypertension, premature deliveryAbstract
A balanced activity of proteolytic enzymes is a prerequisite for the preservation of homeostasis in the intrauterine environment of the fetus. Aminopeptidases produced in the placenta are exopeptidases that remove N-terminal amino acid residues from a polypeptide chain. These proteolytic enzymes differ both in their localization in placental cells and in their substrate specificity. The major biological role of placental aminopeptidases is the inactivation of metabolically active peptides, a process crucial for the control of adverse metabolic changes during pregnancy. The preservation of a placental barrier prevents the transfer of vasoactive peptides produced by the fetus (oxytocin, angiotensin II, vasopressin) to the mother, resulting in the ability to maintain a normal maternal blood pressure, to control uterine contractility, and to prevent preterm delivery. Reduced activity of aminopeptidases in the placenta leads to uncontrolled increases in the transfer of vasoactive peptides to the mother and as a consequence, to vasospasm-associated complications of pregnancy. This paper discusses the physiological role of placental aminopeptidases in normal pregnancy and the involvement of their abnormal activities in complications of pregnancy such as preeclampsia, gestational hypertension or preterm delivery. This is a literature review focusing on articles published in English between 1988 and 2017, and available in PubMed. The following search terms were used: placental proteases, placental aminopeptidases, preeclampsia, gestational hypertension, premature delivery.
Downloads
References
Rawlings ND, Barrett AJ, Finn R. Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 2016, 44(D1), D343-350. DOI: https://doi.org/10.1093/nar/gkv1118
Sanderink GJ, Artur Y, Siest G. Human aminopeptidases: a review of the literature. J Clin Chem Clin Biochem. 1988, 26(12), 795-807. DOI: https://doi.org/10.1515/cclm.1988.26.12.795
Gonzales T, Robert-Baudouy J. Bacterial aminopeptidases: properties and functions. FEMS Microbiol Rev. 1996, 18(4), 319-344. DOI: https://doi.org/10.1111/j.1574-6976.1996.tb00247.x
Gard PR, Fidalgo S, Lotter I, Richardson C, Farina N, Rusted J, Tabet N. Changes of renin-angiotensin system-related aminopeptidases in early stage Alzheimer's disease. Exp Gerontol. 2017, 89, 1-7. DOI: https://doi.org/10.1016/j.exger.2017.01.006
Mizutani S. Physiological roles of placental proteases in feto-placental homeostasis. Nagoya J Med Sci. 1998, 61(3-4), 85-95.
Mizutani S, Tomoda Y. Effects of placental proteases on maternal and fetal blood pressure in normal pregnancy and preeclampsia. Am J Hypertens. 1996, 9(6), 591-597.
Johnson MP, Roten LT, Dyer TD, East CEt, Forsmo S, Blangero J, Brennecke SP, Austgulen R, Moses EK. The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. Hum Genet. 2009, 126(5), 655-666. DOI: https://doi.org/10.1007/s00439-009-0714-x
Horie A, Fujiwara H, Sato Y, Suginami K, Matsumoto H, Maruyama M, Konishi I, Hattori A. Laeverin/aminopeptidase Q induces trophoblast invasion during human early placentation. Hum Reprod. 2012, 27, 1267–1276. DOI: https://doi.org/10.1093/humrep/des068
Nomura M, Tsukahara S, Ando H, Katsumata Y, Okada M, Itakura A, Nomura S, Kikkawa F, Nagasaka T, Mizutani S. Differential distribution of placental leucine aminopeptidase/oxytocinase and aminopeptidase A in human trophoblasts of normal placenta and complete hydatidiform mole. Placenta. 2002, 23(8-9), 631-639. DOI: https://doi.org/10.1053/plac.2002.0861
Nagasaka T, Nomura S, Okamura M, Tsujimoto M, Nakazato H, Oiso Y, Nakashima N, Mizutani S. Immunohistochemical localization of placental leucine aminopeptidase/oxytocinase in normal human placental, fetal and adult tissues. Reprod Fertil Dev. 1997, 9(8), 747-53. DOI: https://doi.org/10.1071/R97055
Mizutani S, Wright JW, Kobayashi H. Placental leucine aminopeptidase- and aminopeptidase A- deficient mice offer insight concerning the mechanisms underlying preterm labor and preeclampsia. J Biomed Biotechnol. 2011, Article ID 286947, 1-12. DOI: https://doi.org/10.1155/2011/286947
Gao J, Marc Y, Iturrioz X, Leroux V, Balavoine F, Llorens-Cortes C. A new strategy for treating hypertension by blocking the activity of the brain renin-angiotensin system with aminopeptidase A inhibitors. Clin Sci 2014, 127(3), 135-148. DOI: https://doi.org/10.1042/CS20130396
Mizutani S, Tomoda Y. Effects of placental proteases on maternal and fetal blood pressure in normal pregnancy and preeclampsia. Am J Hypertens. 1996, 9(6), 591-597. DOI: https://doi.org/10.1016/0895-7061(96)00016-7
Mizutani S, Wright J, Kobayashi H. A new approach regarding the treatment of preeclampsia and preterm labor. Life Sci. 2011, 88(1-2), 17-23. DOI: https://doi.org/10.1016/j.lfs.2010.10.013
Tian C, Huang Z, Wen Z. Associations between serum placental leucine aminopeptidase and pregnancy outcomes. Int J Gynaecol Obstet. 2016, 135(3), 255-258. DOI: https://doi.org/10.1016/j.ijgo.2016.05.016
Toda S, Ando H, Nagasaka T, Tsukahara S, Nomura M, Kotani Y, Nomura S, Kikkawa F, Tsujimoto M, Mizutani S. Existence of placental leucine aminopeptidase/oxytocinase/insulin-regulated membrane aminopeptidase in human endometrial epithelial cells. J Clin Endocrinol Metab. 2002, 87(3), 1384-1389. DOI: https://doi.org/10.1210/jcem.87.3.8306
Matsumoto H, Mori T. Changes in cystine aminopeptidase (oxytocinase) activity in mouse serum, placenta, uterus and liver during pregnancy or after steroid hormone treatments. Zoolog Sci. 1998, 15(1), 111-115. DOI: https://doi.org/10.2108/zsj.15.111
Mizutani S, Naruse K, Hattori A, Tsujimoto M, Kobayashi H. Physiological and pathophysiological roles of placental aminopeptidase in maternal sera: possible relation to preeclampsia and preterm delivery. Expert Opin Med Diagn. 2009, 3(5), 479-491. DOI: https://doi.org/10.1517/17530050903074556
Chauvel EN, Coric P, Llorens-Cortès C, Wilk S, Roques BP, Fournié-Zaluski MC. Investigation of the active site of aminopeptidase A using a series of new thiol-containing inhibitors. J Med Chem. 1994, 37(9), 1339-1346. DOI: https://doi.org/10.1021/jm00035a014
Cilia La Corte AL, Carter AM, Turner AJ, Grant PJ, Hooper NM. The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill. J Renin Angiotensin Aldosterone Syst. 2008, 9(4), 221-225. DOI: https://doi.org/10.1177/1470320308096405
Lee ED. Endoplasmic Reticulum Aminopeptidase 2, a common immunological link to adverse pregnancy outcomes and cancer clearance? Placenta. 2017, 56, 40-43. DOI: https://doi.org/10.1016/j.placenta.2017.03.012
Maruyama M, Hattori A, Goto Y, Ueda M, Maeda M, Fujiwara H, Tsujimoto M. Laeverin/aminopeptidase Q, a novel bestatin-sensitive leucine aminopeptidase belonging to the M1 family of aminopeptidases. J Biol Chem. 2007, 282(28), 20088-20096. DOI: https://doi.org/10.1074/jbc.M702650200
Mizutani S, Goto K, Mizuno K, Itakura A, Kurauchi O, Kikkawa F, Tomoda Y. Interaction between pregnancy-induced bioactive peptides and the placental proteases. Reprod Fertil Dev. 1995, 7(6), 1431-1436. DOI: https://doi.org/10.1071/RD9951431
Landau R, Laverrière A, Bischof P, Irion O, Morales M, Cohen M. Alteration of circulating Placental Leucine Aminopeptidase (P-LAP) activity in preeclampsia. Neuro Endocrinol Lett. 2010, 31(1), 63-66.
Kattah AG, Garovic VD. The management of hypertension in pregnancy. Adv Chronic Kidney Dis. 2013, 20(3), 229-239. DOI: https://doi.org/10.1053/j.ackd.2013.01.014
Etelvino GM, Peluso AA, Santos RA. New components of the renin-angiotensin system: alamandine and the MAS-related G protein-coupled receptor D. Curr Hypertens Rep. 2014, 16(6), 433-439. DOI: https://doi.org/10.1007/s11906-014-0433-0
Morishita R, Higaki J, Okunishi H, Kawamoto T, Ishii K, Nakamura F, Katahira K, Nagano M, Mimami H, Miyazaki M, Ogihara T. Effect of long-term treatment with an angiotensin-converting enzyme inhibitor on the renin-angiotensin system in spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 1991, 18, 685-690. DOI: https://doi.org/10.1111/j.1440-1681.1991.tb01381.x
Goldenberg RL, Goepfert AR, Ramsey PS. Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol. 2005, 192(5 Suppl), S36-46. DOI: https://doi.org/10.1016/j.ajog.2005.02.015
Di Renzo GC, Roura LC, Facchinetti F, Antsaklis A, Breborowicz G, Gratacos E, Husslein P, Lamont R, Mikhailov A, Montenegro N, Radunovic N, Robson M, Robson SC, Sen C, Shennan A, Stamatian F, Ville Y. Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth. J Matern Fetal Neonatal Med. 2011, 24(5), 659-667. DOI: https://doi.org/10.3109/14767058.2011.553694
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Prospects in Pharmaceutical Sciences copyright is retained by the authors. The journal publishes articles in the Open Access policy, within the CC BY 4.0 licence.
This is a human-readable summary of (and not a substitute for) the license. Disclaimer.
You are free to:
Share — copy and redistribute the material in any medium or format
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
How to Cite
