Protective effect of benzothiazole derivative KHG21834 on amyloid β-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons
Abstract We have investigated the effect of KHG21834, a benzothiazole derivative, on the amyloid beta protein (Aβ)-induced cell death in rat pheochromocytoma (PC12) cells and rat cortical and mesencephalic neuron-glia cultures. KHG21834 attenuated the Aβ25-35 -induced apoptotic death in PC12 cells d...
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| Veröffentlicht in: | Toxicology (Amsterdam) 2007-10, Vol.239 (3), p.156-166 |
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| creator | Choi, Myung-Min Kim, Eun-A Hahn, Hoh-Gyu Dal Nam, Kee Yang, Seung-Ju Choi, Soo Young Kim, Tae Ue Cho, Sung-Woo Huh, Jae-Wan |
| description | Abstract We have investigated the effect of KHG21834, a benzothiazole derivative, on the amyloid beta protein (Aβ)-induced cell death in rat pheochromocytoma (PC12) cells and rat cortical and mesencephalic neuron-glia cultures. KHG21834 attenuated the Aβ25-35 -induced apoptotic death in PC12 cells determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL). In the cortical neuron-glia cultures, KHG21834 reduced the Aβ25-35 -induced apoptosis determined by TUNEL staining. Immunocytochemical analysis and Western blot analysis of Aβ25-35 -induced neurotoxicity in mesencephalic neuron-glia cultures with anti-tyrosine hydroxylase (TH) antibody showed that Aβ25-35 decreased the expression of TH protein by 60% and KHG21834 significantly attenuated the Aβ25-35 -induced reduction in the expression of TH. Moreover, KHG21834 attenuates Aβ25-35 -induced toxicity concomitant with the reduction of activation of extracellular signal-regulated kinase (ERK)1/2 to a lesser extent. ERK1 was more sensitively affected than ERK2 in attenuation of Aβ25-35 -induced phosphorylation by KHG21834. These results demonstrated that KHG21834 was capable of protecting neuronal cells from Aβ25-35 -induced degeneration. |
| doi_str_mv | 10.1016/j.tox.2007.07.010 |
| format | Article |
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KHG21834 attenuated the Aβ25-35 -induced apoptotic death in PC12 cells determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL). In the cortical neuron-glia cultures, KHG21834 reduced the Aβ25-35 -induced apoptosis determined by TUNEL staining. Immunocytochemical analysis and Western blot analysis of Aβ25-35 -induced neurotoxicity in mesencephalic neuron-glia cultures with anti-tyrosine hydroxylase (TH) antibody showed that Aβ25-35 decreased the expression of TH protein by 60% and KHG21834 significantly attenuated the Aβ25-35 -induced reduction in the expression of TH. Moreover, KHG21834 attenuates Aβ25-35 -induced toxicity concomitant with the reduction of activation of extracellular signal-regulated kinase (ERK)1/2 to a lesser extent. ERK1 was more sensitively affected than ERK2 in attenuation of Aβ25-35 -induced phosphorylation by KHG21834. These results demonstrated that KHG21834 was capable of protecting neuronal cells from Aβ25-35 -induced degeneration.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/j.tox.2007.07.010</identifier><identifier>PMID: 17714846</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Amyloid beta ; Amyloid beta-Peptides - toxicity ; Animals ; Antibodies - immunology ; Apoptosis - drug effects ; Benzothiazoles - chemistry ; Benzothiazoles - pharmacology ; Biological and medical sciences ; Blotting, Western ; Cell Survival - drug effects ; Cells, Cultured ; Cerebral Cortex - drug effects ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; Cortical neurons ; DNA Fragmentation - drug effects ; Emergency ; ERK ; Immunohistochemistry ; In Situ Nick-End Labeling ; KHG21834 ; Medical sciences ; Mesencephalic neurons ; Mesencephalon - drug effects ; Mesencephalon - metabolism ; Mesencephalon - pathology ; Microscopy, Confocal ; Microscopy, Fluorescence ; Mitogen-Activated Protein Kinase 3 - metabolism ; Molecular Structure ; Neurons - drug effects ; Neurons - metabolism ; Neurons - pathology ; Neuroprotective Agents - chemistry ; Neuroprotective Agents - pharmacology ; PC12 Cells ; Peptide Fragments - toxicity ; Rats ; Rats, Sprague-Dawley ; Toxicology ; Tyrosine 3-Monooxygenase - immunology ; Tyrosine 3-Monooxygenase - metabolism</subject><ispartof>Toxicology (Amsterdam), 2007-10, Vol.239 (3), p.156-166</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2007 Elsevier Ireland Ltd</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-2114b017af68e2ef0eebd69ab435207cf9e6e762f4fac1634563192f261a27023</citedby><cites>FETCH-LOGICAL-c467t-2114b017af68e2ef0eebd69ab435207cf9e6e762f4fac1634563192f261a27023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0300483X07004489$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19061237$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17714846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Myung-Min</creatorcontrib><creatorcontrib>Kim, Eun-A</creatorcontrib><creatorcontrib>Hahn, Hoh-Gyu</creatorcontrib><creatorcontrib>Dal Nam, Kee</creatorcontrib><creatorcontrib>Yang, Seung-Ju</creatorcontrib><creatorcontrib>Choi, Soo Young</creatorcontrib><creatorcontrib>Kim, Tae Ue</creatorcontrib><creatorcontrib>Cho, Sung-Woo</creatorcontrib><creatorcontrib>Huh, Jae-Wan</creatorcontrib><title>Protective effect of benzothiazole derivative KHG21834 on amyloid β-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Abstract We have investigated the effect of KHG21834, a benzothiazole derivative, on the amyloid beta protein (Aβ)-induced cell death in rat pheochromocytoma (PC12) cells and rat cortical and mesencephalic neuron-glia cultures. KHG21834 attenuated the Aβ25-35 -induced apoptotic death in PC12 cells determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL). In the cortical neuron-glia cultures, KHG21834 reduced the Aβ25-35 -induced apoptosis determined by TUNEL staining. Immunocytochemical analysis and Western blot analysis of Aβ25-35 -induced neurotoxicity in mesencephalic neuron-glia cultures with anti-tyrosine hydroxylase (TH) antibody showed that Aβ25-35 decreased the expression of TH protein by 60% and KHG21834 significantly attenuated the Aβ25-35 -induced reduction in the expression of TH. Moreover, KHG21834 attenuates Aβ25-35 -induced toxicity concomitant with the reduction of activation of extracellular signal-regulated kinase (ERK)1/2 to a lesser extent. ERK1 was more sensitively affected than ERK2 in attenuation of Aβ25-35 -induced phosphorylation by KHG21834. These results demonstrated that KHG21834 was capable of protecting neuronal cells from Aβ25-35 -induced degeneration.</description><subject>Amyloid beta</subject><subject>Amyloid beta-Peptides - toxicity</subject><subject>Animals</subject><subject>Antibodies - immunology</subject><subject>Apoptosis - drug effects</subject><subject>Benzothiazoles - chemistry</subject><subject>Benzothiazoles - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - metabolism</subject><subject>Cerebral Cortex - pathology</subject><subject>Cortical neurons</subject><subject>DNA Fragmentation - drug effects</subject><subject>Emergency</subject><subject>ERK</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>KHG21834</subject><subject>Medical sciences</subject><subject>Mesencephalic neurons</subject><subject>Mesencephalon - drug effects</subject><subject>Mesencephalon - metabolism</subject><subject>Mesencephalon - pathology</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Fluorescence</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Molecular Structure</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neuroprotective Agents - chemistry</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>PC12 Cells</subject><subject>Peptide Fragments - toxicity</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Toxicology</subject><subject>Tyrosine 3-Monooxygenase - immunology</subject><subject>Tyrosine 3-Monooxygenase - metabolism</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ksGKFDEQhhtR3NnVB_Aiueitx1Q6k3QjCDLorrjgggreQjpdYTN2J2PSPezsS-y7-CA-k-mdgQUPQkEl8P1F1V9VFC-ALoGCeLNZjuFmySiVyzmAPioWUMumrKBePS4WtKK05HX146Q4TWlDKWUVF0-LE5ASeM3Fori7imFEM7odErQ2v0iwpEV_G8Zrp29Dj6TD6Hb6Hvl8cc6grjgJnuhh3wfXkT-_S-e7yWBHPE65XLhxxo174jy5WgMjBvs-Ee07YkIcndH9_WfAhN7g9lr3zhykPj0rnljdJ3x-zGfF948fvq0vyssv55_W7y9Lw4UcSwbAWwpSW1EjQ0sR2040uuXVilFpbIMCpWCWW21AVHwlKmiYZQI0k9mGs-L1oe42hl8TplENLs2Nao9hSopRXtd1wzMIB9DEkFJEq7bRDTruFVA1b0FtVJ5YzVtQcwDNmpfH4lM7YPegONqegVdHQKdsh43aG5ceuIYKYJXM3NsDh9mKncOoknGzaZ2LeVWqC-6_bbz7R21652f_f-Ie0yZM0WePFajEFFVf53OZr4XKnHndVH8Bv3i73Q</recordid><startdate>20071008</startdate><enddate>20071008</enddate><creator>Choi, Myung-Min</creator><creator>Kim, Eun-A</creator><creator>Hahn, Hoh-Gyu</creator><creator>Dal Nam, Kee</creator><creator>Yang, Seung-Ju</creator><creator>Choi, Soo Young</creator><creator>Kim, Tae Ue</creator><creator>Cho, Sung-Woo</creator><creator>Huh, Jae-Wan</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20071008</creationdate><title>Protective effect of benzothiazole derivative KHG21834 on amyloid β-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons</title><author>Choi, Myung-Min ; Kim, Eun-A ; Hahn, Hoh-Gyu ; Dal Nam, Kee ; Yang, Seung-Ju ; Choi, Soo Young ; Kim, Tae Ue ; Cho, Sung-Woo ; Huh, Jae-Wan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-2114b017af68e2ef0eebd69ab435207cf9e6e762f4fac1634563192f261a27023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Amyloid beta</topic><topic>Amyloid beta-Peptides - toxicity</topic><topic>Animals</topic><topic>Antibodies - immunology</topic><topic>Apoptosis - drug effects</topic><topic>Benzothiazoles - chemistry</topic><topic>Benzothiazoles - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - metabolism</topic><topic>Cerebral Cortex - pathology</topic><topic>Cortical neurons</topic><topic>DNA Fragmentation - drug effects</topic><topic>Emergency</topic><topic>ERK</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>KHG21834</topic><topic>Medical sciences</topic><topic>Mesencephalic neurons</topic><topic>Mesencephalon - drug effects</topic><topic>Mesencephalon - metabolism</topic><topic>Mesencephalon - pathology</topic><topic>Microscopy, Confocal</topic><topic>Microscopy, Fluorescence</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Molecular Structure</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neuroprotective Agents - chemistry</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>PC12 Cells</topic><topic>Peptide Fragments - toxicity</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Toxicology</topic><topic>Tyrosine 3-Monooxygenase - immunology</topic><topic>Tyrosine 3-Monooxygenase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Myung-Min</creatorcontrib><creatorcontrib>Kim, Eun-A</creatorcontrib><creatorcontrib>Hahn, Hoh-Gyu</creatorcontrib><creatorcontrib>Dal Nam, Kee</creatorcontrib><creatorcontrib>Yang, Seung-Ju</creatorcontrib><creatorcontrib>Choi, Soo Young</creatorcontrib><creatorcontrib>Kim, Tae Ue</creatorcontrib><creatorcontrib>Cho, Sung-Woo</creatorcontrib><creatorcontrib>Huh, Jae-Wan</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>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Myung-Min</au><au>Kim, Eun-A</au><au>Hahn, Hoh-Gyu</au><au>Dal Nam, Kee</au><au>Yang, Seung-Ju</au><au>Choi, Soo Young</au><au>Kim, Tae Ue</au><au>Cho, Sung-Woo</au><au>Huh, Jae-Wan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective effect of benzothiazole derivative KHG21834 on amyloid β-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>2007-10-08</date><risdate>2007</risdate><volume>239</volume><issue>3</issue><spage>156</spage><epage>166</epage><pages>156-166</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>Abstract We have investigated the effect of KHG21834, a benzothiazole derivative, on the amyloid beta protein (Aβ)-induced cell death in rat pheochromocytoma (PC12) cells and rat cortical and mesencephalic neuron-glia cultures. KHG21834 attenuated the Aβ25-35 -induced apoptotic death in PC12 cells determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL). In the cortical neuron-glia cultures, KHG21834 reduced the Aβ25-35 -induced apoptosis determined by TUNEL staining. Immunocytochemical analysis and Western blot analysis of Aβ25-35 -induced neurotoxicity in mesencephalic neuron-glia cultures with anti-tyrosine hydroxylase (TH) antibody showed that Aβ25-35 decreased the expression of TH protein by 60% and KHG21834 significantly attenuated the Aβ25-35 -induced reduction in the expression of TH. Moreover, KHG21834 attenuates Aβ25-35 -induced toxicity concomitant with the reduction of activation of extracellular signal-regulated kinase (ERK)1/2 to a lesser extent. ERK1 was more sensitively affected than ERK2 in attenuation of Aβ25-35 -induced phosphorylation by KHG21834. These results demonstrated that KHG21834 was capable of protecting neuronal cells from Aβ25-35 -induced degeneration.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>17714846</pmid><doi>10.1016/j.tox.2007.07.010</doi><tpages>11</tpages></addata></record> |
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| ispartof | Toxicology (Amsterdam), 2007-10, Vol.239 (3), p.156-166 |
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| subjects | Amyloid beta Amyloid beta-Peptides - toxicity Animals Antibodies - immunology Apoptosis - drug effects Benzothiazoles - chemistry Benzothiazoles - pharmacology Biological and medical sciences Blotting, Western Cell Survival - drug effects Cells, Cultured Cerebral Cortex - drug effects Cerebral Cortex - metabolism Cerebral Cortex - pathology Cortical neurons DNA Fragmentation - drug effects Emergency ERK Immunohistochemistry In Situ Nick-End Labeling KHG21834 Medical sciences Mesencephalic neurons Mesencephalon - drug effects Mesencephalon - metabolism Mesencephalon - pathology Microscopy, Confocal Microscopy, Fluorescence Mitogen-Activated Protein Kinase 3 - metabolism Molecular Structure Neurons - drug effects Neurons - metabolism Neurons - pathology Neuroprotective Agents - chemistry Neuroprotective Agents - pharmacology PC12 Cells Peptide Fragments - toxicity Rats Rats, Sprague-Dawley Toxicology Tyrosine 3-Monooxygenase - immunology Tyrosine 3-Monooxygenase - metabolism |
| title | Protective effect of benzothiazole derivative KHG21834 on amyloid β-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons |
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