Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation
Concomitant supplementation of vitamins C and E during pregnancy has been reportedly associated with low birth weight, the premature rupture of membranes and fetal loss or perinatal death in women at risk for preeclampsia; however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR) wit...
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| description | Concomitant supplementation of vitamins C and E during pregnancy has been reportedly associated with low birth weight, the premature rupture of membranes and fetal loss or perinatal death in women at risk for preeclampsia; however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR) within the intervillous space due to abnormal placentation is the mechanism and hypothesize that concomitant administration of aforementioned vitamin antioxidants detrimentally affects trophoblast cells during HR.
Using villous explants, concomitant administration of 50 microM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR.
Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus. |
| doi_str_mv | 10.1371/journal.pone.0012202 |
| format | Article |
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Using villous explants, concomitant administration of 50 microM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR.
Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0012202</identifier><identifier>PMID: 20808946</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antioxidants ; Antioxidants (Nutrients) ; Apoptosis ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins - metabolism ; Ascorbic Acid - pharmacology ; Autophagy ; Autophagy - drug effects ; bcl-2 Homologous Antagonist-Killer Protein - genetics ; bcl-2 Homologous Antagonist-Killer Protein - metabolism ; Bcl-2 protein ; Bcl-x protein ; bcl-X Protein - genetics ; bcl-X Protein - metabolism ; Beclin-1 ; Birth weight ; Cell culture ; Cell death ; Cell Hypoxia ; Chorionic Villi - drug effects ; Chorionic Villi - metabolism ; Clinical trials ; Clinical Trials as Topic ; Cytokines ; Cytosol - drug effects ; Cytosol - metabolism ; Drug Synergism ; Enzymes ; Explants ; Female ; Fetuses ; Growth factors ; Gynecology ; Humans ; Hypoxia ; Infant mortality ; Kinases ; Low birth weight ; Membrane Proteins - metabolism ; Membranes ; Microtubule-Associated Proteins - metabolism ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Obstetrics ; Obstetrics/Hypertensive Disorders ; Obstetrics/Management of High-Risk Pregnancies ; Obstetrics/Pregnancy ; Oxidative stress ; Oxygen ; Oxygen - metabolism ; Phagocytosis ; Phosphorylation ; Placenta ; Pre-eclampsia ; Preeclampsia ; Pregnancy ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Supplementation ; Supplements ; Transcription, Genetic - drug effects ; Trophoblasts ; Trophoblasts - cytology ; Trophoblasts - drug effects ; Trophoblasts - metabolism ; Vitamin C ; Vitamin E - pharmacology ; Vitamins</subject><ispartof>PloS one, 2010-08, Vol.5 (8), p.e12202</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Hung et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Hung et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-de71ceda794b15f28f29d1ec006d8314080e4a1a355cffe7b060a37dd20edf3d3</citedby><cites>FETCH-LOGICAL-c757t-de71ceda794b15f28f29d1ec006d8314080e4a1a355cffe7b060a37dd20edf3d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922378/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922378/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20808946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hung, Tai-Ho</creatorcontrib><creatorcontrib>Chen, Szu-Fu</creatorcontrib><creatorcontrib>Li, Meng-Jen</creatorcontrib><creatorcontrib>Yeh, Yi-Lin</creatorcontrib><creatorcontrib>Hsieh, T'sang-T'ang</creatorcontrib><title>Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Concomitant supplementation of vitamins C and E during pregnancy has been reportedly associated with low birth weight, the premature rupture of membranes and fetal loss or perinatal death in women at risk for preeclampsia; however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR) within the intervillous space due to abnormal placentation is the mechanism and hypothesize that concomitant administration of aforementioned vitamin antioxidants detrimentally affects trophoblast cells during HR.
Using villous explants, concomitant administration of 50 microM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR.
Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus.</description><subject>Analysis</subject><subject>Antioxidants</subject><subject>Antioxidants (Nutrients)</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Ascorbic Acid - pharmacology</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>bcl-2 Homologous Antagonist-Killer Protein - genetics</subject><subject>bcl-2 Homologous Antagonist-Killer Protein - metabolism</subject><subject>Bcl-2 protein</subject><subject>Bcl-x protein</subject><subject>bcl-X Protein - genetics</subject><subject>bcl-X Protein - metabolism</subject><subject>Beclin-1</subject><subject>Birth weight</subject><subject>Cell culture</subject><subject>Cell death</subject><subject>Cell Hypoxia</subject><subject>Chorionic Villi - drug effects</subject><subject>Chorionic Villi - metabolism</subject><subject>Clinical trials</subject><subject>Clinical Trials as Topic</subject><subject>Cytokines</subject><subject>Cytosol - drug effects</subject><subject>Cytosol - metabolism</subject><subject>Drug Synergism</subject><subject>Enzymes</subject><subject>Explants</subject><subject>Female</subject><subject>Fetuses</subject><subject>Growth factors</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Infant mortality</subject><subject>Kinases</subject><subject>Low birth weight</subject><subject>Membrane Proteins - metabolism</subject><subject>Membranes</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Obstetrics</subject><subject>Obstetrics/Hypertensive Disorders</subject><subject>Obstetrics/Management of High-Risk Pregnancies</subject><subject>Obstetrics/Pregnancy</subject><subject>Oxidative stress</subject><subject>Oxygen</subject><subject>Oxygen - metabolism</subject><subject>Phagocytosis</subject><subject>Phosphorylation</subject><subject>Placenta</subject><subject>Pre-eclampsia</subject><subject>Preeclampsia</subject><subject>Pregnancy</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Supplementation</subject><subject>Supplements</subject><subject>Transcription, Genetic - drug effects</subject><subject>Trophoblasts</subject><subject>Trophoblasts - cytology</subject><subject>Trophoblasts - drug effects</subject><subject>Trophoblasts - metabolism</subject><subject>Vitamin C</subject><subject>Vitamin E - pharmacology</subject><subject>Vitamins</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QDguDFjPno542wjKsOLCz4dRvS5mQmQ5t0k3Sd-RH-ZzMz3WUKCtKLnpzznLfJ25wkeUnwnLCCvN_YwRnRzntrYI4xoRTTR8k5qRid5RSzxyfxWfLM-w3GGSvz_GlyRnGJyyrNz5PfH7VS4MAELVoEMW6CR1ahxprGdjoIE9DgYZ-6i6tOG48WSBiJrpA1KDjbr23dCh-Q6G0frNf-UBZDiCWx2qEawi8Ag4x1nd1qcSivd_0-njmw290KjAjamufJEyVaDy_G90Xy49PV98WX2fXN5-Xi8nrWFFkRZhIK0oAURZXWJFO0VLSSBBqMc1kyksbTQSqIYFnWxBMVNc6xYIWUFINUTLKL5PVRt2-t56OTnhNGyoqlVYYjsTwS0ooN753uhNtxKzQ_JKxbceGCblrgoHJS1TiVZcbSTEH0tcwLVecZISWkELU-jF8b6g5kE812op2ITitGr_nK3nFaUcqKMgq8GQWcvR3Ah39seaRWIu5KG2WjWNNp3_DLtGBlkROcRmr-Fyo-EjodfzooHfOThneThsgE2IaVGLzny29f_5-9-Tll356waxBtWHvbDvt74KdgegQbZ713oB6cI5jvR-HeDb4fBT6OQmx7der6Q9P93Wd_AMa3Bzg</recordid><startdate>20100816</startdate><enddate>20100816</enddate><creator>Hung, Tai-Ho</creator><creator>Chen, Szu-Fu</creator><creator>Li, Meng-Jen</creator><creator>Yeh, Yi-Lin</creator><creator>Hsieh, T'sang-T'ang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100816</creationdate><title>Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation</title><author>Hung, Tai-Ho ; Chen, Szu-Fu ; Li, Meng-Jen ; Yeh, Yi-Lin ; Hsieh, T'sang-T'ang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-de71ceda794b15f28f29d1ec006d8314080e4a1a355cffe7b060a37dd20edf3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Analysis</topic><topic>Antioxidants</topic><topic>Antioxidants (Nutrients)</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Ascorbic Acid - pharmacology</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>bcl-2 Homologous Antagonist-Killer Protein - genetics</topic><topic>bcl-2 Homologous Antagonist-Killer Protein - metabolism</topic><topic>Bcl-2 protein</topic><topic>Bcl-x protein</topic><topic>bcl-X Protein - genetics</topic><topic>bcl-X Protein - metabolism</topic><topic>Beclin-1</topic><topic>Birth weight</topic><topic>Cell culture</topic><topic>Cell death</topic><topic>Cell Hypoxia</topic><topic>Chorionic Villi - drug effects</topic><topic>Chorionic Villi - metabolism</topic><topic>Clinical trials</topic><topic>Clinical Trials as Topic</topic><topic>Cytokines</topic><topic>Cytosol - drug effects</topic><topic>Cytosol - metabolism</topic><topic>Drug Synergism</topic><topic>Enzymes</topic><topic>Explants</topic><topic>Female</topic><topic>Fetuses</topic><topic>Growth factors</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Infant mortality</topic><topic>Kinases</topic><topic>Low birth weight</topic><topic>Membrane Proteins - 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We surmise that hypoxia-reoxygenation (HR) within the intervillous space due to abnormal placentation is the mechanism and hypothesize that concomitant administration of aforementioned vitamin antioxidants detrimentally affects trophoblast cells during HR.
Using villous explants, concomitant administration of 50 microM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR.
Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20808946</pmid><doi>10.1371/journal.pone.0012202</doi><tpages>e12202</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1318934950 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Antioxidants Antioxidants (Nutrients) Apoptosis Apoptosis - drug effects Apoptosis Regulatory Proteins - metabolism Ascorbic Acid - pharmacology Autophagy Autophagy - drug effects bcl-2 Homologous Antagonist-Killer Protein - genetics bcl-2 Homologous Antagonist-Killer Protein - metabolism Bcl-2 protein Bcl-x protein bcl-X Protein - genetics bcl-X Protein - metabolism Beclin-1 Birth weight Cell culture Cell death Cell Hypoxia Chorionic Villi - drug effects Chorionic Villi - metabolism Clinical trials Clinical Trials as Topic Cytokines Cytosol - drug effects Cytosol - metabolism Drug Synergism Enzymes Explants Female Fetuses Growth factors Gynecology Humans Hypoxia Infant mortality Kinases Low birth weight Membrane Proteins - metabolism Membranes Microtubule-Associated Proteins - metabolism Mitochondria Mitochondria - drug effects Mitochondria - metabolism Obstetrics Obstetrics/Hypertensive Disorders Obstetrics/Management of High-Risk Pregnancies Obstetrics/Pregnancy Oxidative stress Oxygen Oxygen - metabolism Phagocytosis Phosphorylation Placenta Pre-eclampsia Preeclampsia Pregnancy Proteins Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Supplementation Supplements Transcription, Genetic - drug effects Trophoblasts Trophoblasts - cytology Trophoblasts - drug effects Trophoblasts - metabolism Vitamin C Vitamin E - pharmacology Vitamins |
| title | Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T10%3A15%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Differential%20effects%20of%20concomitant%20use%20of%20vitamins%20C%20and%20E%20on%20trophoblast%20apoptosis%20and%20autophagy%20between%20normoxia%20and%20hypoxia-reoxygenation&rft.jtitle=PloS%20one&rft.au=Hung,%20Tai-Ho&rft.date=2010-08-16&rft.volume=5&rft.issue=8&rft.spage=e12202&rft.pages=e12202-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0012202&rft_dat=%3Cgale_plos_%3EA473876104%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1318934950&rft_id=info:pmid/20808946&rft_galeid=A473876104&rft_doaj_id=oai_doaj_org_article_ef619b04d85345fe946867fb65118e4e&rfr_iscdi=true |