DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Dong-Myung | ko |
dc.contributor.author | Ryu, Seung-Wook | ko |
dc.contributor.author | Choi, Chulhee | ko |
dc.date.accessioned | 2013-03-09T17:06:29Z | - |
dc.date.available | 2013-03-09T17:06:29Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2010-12 | - |
dc.identifier.citation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.403, no.1, pp.91 - 96 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | http://hdl.handle.net/10203/96952 | - |
dc.description.abstract | Despite the well established anti-cancer effect of farnesyltransferase inhibitor FTI-277, the neurotoxic effects of the agent are not yet clearly defined at the molecular and cellular levels. Here, we report the neurotoxic effects of FTI-277 and the involvement of reactive oxygen species (ROS) in FTI-induced neurotoxicity. Although there is no significant effect of FTI-277 for 2 days, long-term treatment of FTI-277 for 4 days induced dramatic reduction in outgrowth, maturation and branching of neuritis and considerable cytoxicity in a dose- and time-dependent manner in primary cultured rat embryo hippocampal neurons. Interestingly, FTI-277 for 4 days dramatically decreased expression of synapsin I, a crucial molecule involved in the neuronal growth and plasticity, and increased a cytotoxic G-protein RhoB of which ectopic expression induced the neurotoxicity in hippocampal neurons. Moreover, treatment with FTI-277 dramatically increased intracellular levels of ROS, which was sustained for 4 days; while blockage of ROS rescued FTI-277-induced neurotoxicity as well as both decrease of synapsin I and increase of RhoB. Taken together, these results provide the molecular insights for the mechanisms which might be of use aiming for avoiding neurotoxic side effects by FTI agent for a drug development for a clinical use. (C) 2010 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.subject | FARNESYL TRANSFERASE INHIBITORS | - |
dc.subject | MYELOID-LEUKEMIA CELLS | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | INDUCED APOPTOSIS | - |
dc.subject | JNK ACTIVATION | - |
dc.subject | CANCER-CELLS | - |
dc.subject | RHOB | - |
dc.subject | IMPAIRMENT | - |
dc.subject | EXPRESSION | - |
dc.subject | PLASTICITY | - |
dc.title | Long-term treatment of farnesyltransferase inhibitor FTI-277 induces neurotoxicity of hippocampal neurons from rat embryo in a ROS-dependent manner | - |
dc.type | Article | - |
dc.identifier.wosid | 000285226500016 | - |
dc.identifier.scopusid | 2-s2.0-78649718062 | - |
dc.type.rims | ART | - |
dc.citation.volume | 403 | - |
dc.citation.issue | 1 | - |
dc.citation.beginningpage | 91 | - |
dc.citation.endingpage | 96 | - |
dc.citation.publicationname | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.identifier.doi | 10.1016/j.bbrc.2010.10.123 | - |
dc.contributor.localauthor | Choi, Chulhee | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Farnesyltransferase inhibitor | - |
dc.subject.keywordAuthor | Hippocampal neurons | - |
dc.subject.keywordAuthor | Neurodegeneracy | - |
dc.subject.keywordAuthor | Reactive oxygen species | - |
dc.subject.keywordPlus | FARNESYL TRANSFERASE INHIBITORS | - |
dc.subject.keywordPlus | MYELOID-LEUKEMIA CELLS | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | JNK ACTIVATION | - |
dc.subject.keywordPlus | CANCER-CELLS | - |
dc.subject.keywordPlus | RHOB | - |
dc.subject.keywordPlus | IMPAIRMENT | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PLASTICITY | - |
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