The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New Analog
We synthesized an estrogen analog, ZYC-5, lacking activity at the classical estrogen receptor and examined its neuroprotective potential against necrosis induced by N-methyl-d-aspartate (NMDA) and apoptosis/necrosis induced by the NMDA receptor antagonist (+)-3-(2-carboxypiperazine-4-yl)-propyl-1-ph...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2002-04-01
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| Series: | Neurobiology of Disease |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610290478X |
| _version_ | 1818563603384500224 |
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| author | Shuli Xia Zu Yun Cai Liu Lin Thio Jeong Sook Kim-Han Laura L. Dugan Douglas F. Covey Steven M. Rothman |
| author_facet | Shuli Xia Zu Yun Cai Liu Lin Thio Jeong Sook Kim-Han Laura L. Dugan Douglas F. Covey Steven M. Rothman |
| author_sort | Shuli Xia |
| collection | DOAJ |
| description | We synthesized an estrogen analog, ZYC-5, lacking activity at the classical estrogen receptor and examined its neuroprotective potential against necrosis induced by N-methyl-d-aspartate (NMDA) and apoptosis/necrosis induced by the NMDA receptor antagonist (+)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). ZYC-5 protected cortical neurons in a dose-dependent manner, and the neuroprotection was more robust than with 17β-estradiol. The effect of ZYC-5 was not mediated by the classical estrogen receptor, because it was unaffected by the antagonists 4-hydroxytamoxifen and ICI 182,780. The ZYC-5 protection against excitotoxicity was not directly mediated through the NMDA receptor, because there was no effect of ZYC-5 on NMDA current or the intracellular calcium increase induced by NMDA. Results obtained with the free-radical-sensitive dye, dihydroethidium, suggested that the neuroprotection of ZYC-5 was partly related to its radical scavenging properties. Although some of estrogen's neuroprotective effects may depend upon the estrogen receptor, our results suggest the possibility of neuroprotection without hormonal side effects. |
| first_indexed | 2024-12-14T01:18:34Z |
| format | Article |
| id | doaj.art-4d50ae677f1c41dfb513448688d11746 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T01:18:34Z |
| publishDate | 2002-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-4d50ae677f1c41dfb513448688d117462022-12-21T23:22:30ZengElsevierNeurobiology of Disease1095-953X2002-04-0193282293The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New AnalogShuli Xia0Zu Yun Cai1Liu Lin Thio2Jeong Sook Kim-Han3Laura L. Dugan4Douglas F. Covey5Steven M. Rothman6Department of Neurology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Neurology, St. Louis Children's Hospital, St. Louis, Missouri, 63110Department of Neurology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Neurology, St. Louis Children's Hospital, St. Louis, Missouri, 63110Department of Neurology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Neurology, St. Louis Children's Hospital, St. Louis, Missouri, 63110Department of Neurology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Neurology, St. Louis Children's Hospital, St. Louis, Missouri, 63110Department of Neurology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Neurology, St. Louis Children's Hospital, St. Louis, Missouri, 63110Department of Neurology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Neurology, St. Louis Children's Hospital, St. Louis, Missouri, 63110Department of Neurology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Mssouri, 63110; Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Mssouri, 63110; Department of Neurology, St. Louis Children's Hospital, St. Louis, Missouri, 63110We synthesized an estrogen analog, ZYC-5, lacking activity at the classical estrogen receptor and examined its neuroprotective potential against necrosis induced by N-methyl-d-aspartate (NMDA) and apoptosis/necrosis induced by the NMDA receptor antagonist (+)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). ZYC-5 protected cortical neurons in a dose-dependent manner, and the neuroprotection was more robust than with 17β-estradiol. The effect of ZYC-5 was not mediated by the classical estrogen receptor, because it was unaffected by the antagonists 4-hydroxytamoxifen and ICI 182,780. The ZYC-5 protection against excitotoxicity was not directly mediated through the NMDA receptor, because there was no effect of ZYC-5 on NMDA current or the intracellular calcium increase induced by NMDA. Results obtained with the free-radical-sensitive dye, dihydroethidium, suggested that the neuroprotection of ZYC-5 was partly related to its radical scavenging properties. Although some of estrogen's neuroprotective effects may depend upon the estrogen receptor, our results suggest the possibility of neuroprotection without hormonal side effects.http://www.sciencedirect.com/science/article/pii/S096999610290478X |
| spellingShingle | Shuli Xia Zu Yun Cai Liu Lin Thio Jeong Sook Kim-Han Laura L. Dugan Douglas F. Covey Steven M. Rothman The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New Analog Neurobiology of Disease |
| title | The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New Analog |
| title_full | The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New Analog |
| title_fullStr | The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New Analog |
| title_full_unstemmed | The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New Analog |
| title_short | The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence from a New Analog |
| title_sort | estrogen receptor is not essential for all estrogen neuroprotection new evidence from a new analog |
| url | http://www.sciencedirect.com/science/article/pii/S096999610290478X |
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