| Inhibition of LPS-induced apoptosis in differentiated-PC12 cells by new triazine derivatives through NF-κB-mediated suppression of COX-2. | |
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MedLine Citation:
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PMID: 20946929 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Anti-inflammatory therapy approaches have been in the focus of attention in the treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). In this study, we examined the role of new 1,2,4-triazine derivatives against cytotoxicity exerted by lipopolysaccharide (LPS) in differentiated rat pheochromocytoma (PC12) cell line. Our results indicated that LPS-induced cell death can be inhibited in the presence of some of these compounds, as measured by MTT test, acridine orange/ethidium bromide staining and caspase-3 expression assay. We further showed that these compounds exert their protective effects through the inhibition of LPS-induced generation of nitric oxide and reactive oxygen species. Triazine derivatives inhibited LPS-induced nuclear translocation of nuclear factor- κB, a known regulator of a host of genes involved in specific stress and inflammatory responses. Pretreatment of PC12 cells with triazine derivatives also suppressed LPS-induced cyclooxygenase-2 expression while up-regulated heat shock protein-70 (Hsp-70). Moreover, the treatment of brain diseases is limited by the insufficiency in delivering therapeutic drugs into brain relating to highly limited transport of compounds through blood-brain barrier (BBB). Using a reliable model based on the artificial neural network, we indicated that these compounds are capable of penetrating BBB and may be useful agents for preventing neuroinflammatory diseases like AD. |
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Authors:
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Niloufar Ansari; Fariba Khodagholi; Mahmoudreza Ramin; Mohsen Amini; Hamid Irannejad; Leila Dargahi; Azim Dehghani Amirabad |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-12 |
Journal Detail:
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Title: Neurochemistry international Volume: 57 ISSN: 1872-9754 ISO Abbreviation: Neurochem. Int. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8006959 Medline TA: Neurochem Int Country: England |
Other Details:
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Languages: eng Pagination: 958-68 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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