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Involvement of Monocarboxylate Transporter 4 Expression in Statin-Induced Cytotoxicity
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
| Title: | Involvement of Monocarboxylate Transporter 4 Expression in Statin-Induced Cytotoxicity |
| Authors: | Kikutani, Yurika Browse this author | | Kobayashi, Masaki Browse this author →KAKEN DB | | Konishi, Toru Browse this author | | Sasaki, Shotaro Browse this author | | Narumi, Katsuya Browse this author | | Furugen, Ayako Browse this author | | Takahashi, Natsuko Browse this author →KAKEN DB | | Iseki, Ken Browse this author →KAKEN DB |
| Keywords: | monocarboxylate transporter 4 | | statin | | cytotoxicity |
| Issue Date: | Apr-2016 |
| Publisher: | Elsevier |
| Journal Title: | Journal of Pharmaceutical Sciences |
| Volume: | 105 |
| Issue: | 4 |
| Start Page: | 1544 |
| End Page: | 1549 |
| Publisher DOI: | 10.1016/j.xphs.2016.01.014 |
| PMID: | 26935883 |
| Abstract: | Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the most widely used cholesterol-lowering agents for prevention of obstructive cardiovascular events. However, statins can cause a variety of skeletal muscle problems, and exercise leads to an increase in statin-induced muscle injury. Exercise induces the protein content of monocarboxylate transporter 4 (MCT4), which is expressed strongly in skeletal muscle and is thought to play a major role in the transport of metabolically important monocarboxylates such as L-lactate. We previously reported that alpha-cyano-4-hydroxycinnamate, an MCT4 inhibitor, increased the inhibition of growth of RD cells, a prototypic embryonal rhabdomyosarcoma cell line (an RD cell line), as a model of in vitro skeletal muscle, induced by a statin. However, it is unclear whether statin-induced RD cell cytotoxicity is associated with MCT4 expression. We, therefore, examined the relationship between statin-induced cytotoxicity and MCT4 expression in RD cells. Atorvastatin reduced the number of viable cells and upregulated MCT4, but not MCT1, mRNA level in a concentration-dependent manner. MCT4 knockdown suppressed atorvastatin-, simvastatin-, and fluvastatin-induced reduction of cell viability and apoptosis compared with negative controletreated cells. In this study, we demonstrated that MCT4 expression is associated with statin-induced cytotoxicity. (C) 2016 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. |
| Rights: | © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/64942 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 小林 正紀
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