open access

https://hdl.handle.net/2115/64942

Involvement of Monocarboxylate Transporter 4 Expression in Statin-Induced Cytotoxicity

英語

cytotoxicity

2016-04

Elsevier

Journal of Pharmaceutical Sciences

105(4)

1544-1549

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.

学術雑誌論文

Submitted Manuscript Under Review

Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

© 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/

0022-3549