Abstract：
:The effects of tournefolic acid B (TAB) and two ester derivatives, TAB methyl ester (TABM) and TAB ethyl ester (TABE), on N-methyl-D-aspartate (NMDA)-mediated excitotoxicity and the underlying mechanisms were investigated. Treatment with 50 microM NMDA elicited neuronal death by 48.7 +/- 5.1%, coinciding with the appearance of injured morphology. TABM (50 microM) attenuated the NMDA-induced cell death by 60.9 +/- 19.7%, and to a lesser extent by TABE. The NMDA-mediated activation of calpain was not affected by TABM and TABE, as determined by the cleavage of alpha-spectrin. NMDA increased the activity of caspases 2, 3, 6, 8, and 9 and reached the maximum after 8-h treatment. TABM and TABE abrogated NMDA-induced activation of caspases 2, 3, 6, and 8 by approximately 80 to 90% and 50 to 60%, respectively, and to a higher extent for caspase 9. TABM and TABE also blocked the NMDA-mediated activation of caspase 12. Furthermore, TABM and TABE eliminated the NMDA-induced accumulation of superoxide anion (O2-*). NMDA evoked significant depolarization of mitochondria, whereas TABM elicited a mild decrease of mitochondrial membrane potential as determined by tetramethylrhodamine methyl ester perchlorate. NMDA treatment induced elevation of Ca2+ levels in cytosol, endoplasmic reticulum (ER), and mitochondria. TABM (50 microM) significantly diminished the NMDA-induced elevation of Ca2+ levels in mitochondria and ER but not cytosol. Therefore, TABM decreased mitochondrial membrane potential and attenuated the NMDA-mediated Ca2+-loading in ER and mitochondria. These events subsequently eliminated the accumulation of O2-* and blocked the activation of caspase cascade, thereby conferring their neuroprotective effects on NMDA-mediated excitotoxicity.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Wang CN,Pan HC,Lin YL,Chi CW,Shiao YJdoi
10.1124/mol.105.018770keywords:
subject
Has Abstractpub_date
2006-03-01 00:00:00pages
950-9issue
3eissn
0026-895Xissn
1521-0111pii
mol.105.018770journal_volume
69pub_type
杂志文章abstract：:The nucleoside analogue, 3-deazaadenosine (c3-Ado), serves both as a substrate and as an inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, and the ability of this compound to induce accumulation of intracellular AdoHcy and S-3-deazaadenosylhomocysteine (c3-AdoHcy) in various cells and species has been widely doc...
journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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更新日期：1995-12-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1990-06-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1990-02-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
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journal_title：Molecular pharmacology
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doi：
更新日期：1996-04-01 00:00:00
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doi：
更新日期：1998-05-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1994-05-01 00:00:00
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doi：
更新日期：1984-01-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
更新日期：1988-02-01 00:00:00
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journal_title：Molecular pharmacology
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doi：
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