The expression and activity of prostaglandin h synthase-2 is enhanced in trophoblast from women with preeclampsia

Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in placental villi. The two isozymes of prostaglandin H synthase (PGHS) are essential for prostanoid synthesis. We tested the hypothesis that PGHS-2 expression is elevated in trophoblast from preeclamptic women, compared...

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Veröffentlicht in:The journal of clinical endocrinology and metabolism 1997-09, Vol.82 (9), p.3059-3062
Hauptverfasser: JOHNSON, R. D, SADOVSKY, Y, GRAHAM, C, ANTEBY, E. Y, POLAKOSKI, K. L, HUANG, X, NELSON, D. M
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container_end_page 3062
container_issue 9
container_start_page 3059
container_title The journal of clinical endocrinology and metabolism
container_volume 82
creator JOHNSON, R. D
SADOVSKY, Y
GRAHAM, C
ANTEBY, E. Y
POLAKOSKI, K. L
HUANG, X
NELSON, D. M
description Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in placental villi. The two isozymes of prostaglandin H synthase (PGHS) are essential for prostanoid synthesis. We tested the hypothesis that PGHS-2 expression is elevated in trophoblast from preeclamptic women, compared with trophoblast from healthy women. Using immunofluorescent staining, we demonstrated a higher PGHS-2 expression in villi from preeclampsia, compared with normal pregnancy. Cytotrophoblasts cultured from placentas of preeclamptic women expressed higher levels of PGHS-2 compared with cytotrophoblasts from normal placentas. This enhanced expression of PGHS-2 correlated with increased media levels of both thromboxane and prostaglandin E2, two products of PGHS activity. The increased prostanoid production by trophoblast from preeclamptic women was markedly reduced by NS-398, a specific inhibitor of PGHS-2. We conclude that both expression and activity of PGHS-2 are enhanced in trophoblasts from preeclamptic women compared with trophoblast from normal pregnancies. The increased production of prostanoids may contribute to the clinical syndrome of preeclampsia. Our data suggest that a selective inhibitor of PGHS-2 might provide a therapeutic alternative to prophylactic low-dose aspirin in modifying the prostanoid profile in preeclampsia.
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This enhanced expression of PGHS-2 correlated with increased media levels of both thromboxane and prostaglandin E2, two products of PGHS activity. The increased prostanoid production by trophoblast from preeclamptic women was markedly reduced by NS-398, a specific inhibitor of PGHS-2. We conclude that both expression and activity of PGHS-2 are enhanced in trophoblasts from preeclamptic women compared with trophoblast from normal pregnancies. The increased production of prostanoids may contribute to the clinical syndrome of preeclampsia. 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D</creatorcontrib><creatorcontrib>SADOVSKY, Y</creatorcontrib><creatorcontrib>GRAHAM, C</creatorcontrib><creatorcontrib>ANTEBY, E. Y</creatorcontrib><creatorcontrib>POLAKOSKI, K. L</creatorcontrib><creatorcontrib>HUANG, X</creatorcontrib><creatorcontrib>NELSON, D. M</creatorcontrib><title>The expression and activity of prostaglandin h synthase-2 is enhanced in trophoblast from women with preeclampsia</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in placental villi. The two isozymes of prostaglandin H synthase (PGHS) are essential for prostanoid synthesis. We tested the hypothesis that PGHS-2 expression is elevated in trophoblast from preeclamptic women, compared with trophoblast from healthy women. 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Obstetrics</subject><subject>Humans</subject><subject>Isoenzymes - antagonists &amp; inhibitors</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Medical sciences</subject><subject>Nitrobenzenes - pharmacology</subject><subject>Placenta - cytology</subject><subject>Placenta - enzymology</subject><subject>Pre-Eclampsia - enzymology</subject><subject>Pregnancy</subject><subject>Pregnancy. Fetus. 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Obstetrics</topic><topic>Humans</topic><topic>Isoenzymes - antagonists &amp; inhibitors</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Medical sciences</topic><topic>Nitrobenzenes - pharmacology</topic><topic>Placenta - cytology</topic><topic>Placenta - enzymology</topic><topic>Pre-Eclampsia - enzymology</topic><topic>Pregnancy</topic><topic>Pregnancy. Fetus. Placenta</topic><topic>Prostaglandin-Endoperoxide Synthases - adverse effects</topic><topic>Prostaglandin-Endoperoxide Synthases - genetics</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Reference Values</topic><topic>RNA, Messenger - metabolism</topic><topic>Sulfonamides - pharmacology</topic><topic>Trophoblasts - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JOHNSON, R. D</creatorcontrib><creatorcontrib>SADOVSKY, Y</creatorcontrib><creatorcontrib>GRAHAM, C</creatorcontrib><creatorcontrib>ANTEBY, E. Y</creatorcontrib><creatorcontrib>POLAKOSKI, K. L</creatorcontrib><creatorcontrib>HUANG, X</creatorcontrib><creatorcontrib>NELSON, D. M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JOHNSON, R. D</au><au>SADOVSKY, Y</au><au>GRAHAM, C</au><au>ANTEBY, E. Y</au><au>POLAKOSKI, K. L</au><au>HUANG, X</au><au>NELSON, D. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The expression and activity of prostaglandin h synthase-2 is enhanced in trophoblast from women with preeclampsia</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>1997-09-01</date><risdate>1997</risdate><volume>82</volume><issue>9</issue><spage>3059</spage><epage>3062</epage><pages>3059-3062</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in placental villi. The two isozymes of prostaglandin H synthase (PGHS) are essential for prostanoid synthesis. We tested the hypothesis that PGHS-2 expression is elevated in trophoblast from preeclamptic women, compared with trophoblast from healthy women. Using immunofluorescent staining, we demonstrated a higher PGHS-2 expression in villi from preeclampsia, compared with normal pregnancy. Cytotrophoblasts cultured from placentas of preeclamptic women expressed higher levels of PGHS-2 compared with cytotrophoblasts from normal placentas. This enhanced expression of PGHS-2 correlated with increased media levels of both thromboxane and prostaglandin E2, two products of PGHS activity. The increased prostanoid production by trophoblast from preeclamptic women was markedly reduced by NS-398, a specific inhibitor of PGHS-2. We conclude that both expression and activity of PGHS-2 are enhanced in trophoblasts from preeclamptic women compared with trophoblast from normal pregnancies. The increased production of prostanoids may contribute to the clinical syndrome of preeclampsia. Our data suggest that a selective inhibitor of PGHS-2 might provide a therapeutic alternative to prophylactic low-dose aspirin in modifying the prostanoid profile in preeclampsia.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>9284743</pmid><doi>10.1210/jc.82.9.3059</doi><tpages>4</tpages></addata></record>
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current)
subjects Biological and medical sciences
Blotting, Northern
Blotting, Western
Cells, Cultured
Cyclooxygenase Inhibitors - pharmacology
Diseases of mother, fetus and pregnancy
Female
Fluorescent Antibody Technique
Gynecology. Andrology. Obstetrics
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - genetics
Isoenzymes - metabolism
Medical sciences
Nitrobenzenes - pharmacology
Placenta - cytology
Placenta - enzymology
Pre-Eclampsia - enzymology
Pregnancy
Pregnancy. Fetus. Placenta
Prostaglandin-Endoperoxide Synthases - adverse effects
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandin-Endoperoxide Synthases - metabolism
Reference Values
RNA, Messenger - metabolism
Sulfonamides - pharmacology
Trophoblasts - enzymology
title The expression and activity of prostaglandin h synthase-2 is enhanced in trophoblast from women with preeclampsia
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