Hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma cells

被引：56

作者：

Araki, Makoto ^{[1
]}

Motojima, Kiyoto ^{[1
]}

机构：

[1] Meiji Pharmaceut Univ, Dept Biochem, Tokyo 2048588, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 367卷 / 02期

基金：

日本学术振兴会;

关键词：

statin; autophagy; myopathy; rhabdomyolysis; rhabdomyosarcoma;

D O I：

10.1016/j.bbrc.2007.12.166

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Statins are widely used to treat hypercholesterolemia, but they are associated with muscle-related adverse events, by as yet, inadequately resolved mechanisms. In this study, we report that statins induced autophagy in cultured human rhabdomyosarcoma A204 cells. Potency differed widely among the statins: cerivastatin induced autophagy at 0.1 mu M, simvastatin at 10 mu M but none was induced by pravastatin. Addition of mevalonate, but not cholesterol, blocked induction of autophagy by cerivastatin, suggesting that this induction is dependent on modulation of isoprenoid metabolic pathways. The statin-induced autophagy was not observed in other types of cells, such as human hepatoma HepG2 or embryonic kidney HEK293 cells. Muscle-specific abortive induction of autophagy by hydrophobic statins is a possible mechanism for statin-induced muscle-related side effects. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：462 / 467

页数：6

共 24 条

[1] Identification of ERRα as a specific partner of PGC-1α for the activation of PDK4 gene expression in muscle [J].

Araki, M ;

Motojima, K .

FEBS JOURNAL, 2006, 273 (08) :1669-1680

[2] Statin-induced myopathy: The two faces of Janus [J].

Arora, Rohit ;

Liebo, Max ;

Maldonado, Frank .

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, 2006, 11 (02) :105-112

[3] Cholesterol depletion induces autophagy [J].

Cheng, Jinglei ;

Ohsaki, Yuki ;

Tauchi-Sato, Kumi ;

Fujita, Akikazu ;

Fujimoto, Toyoshi .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 351 (01) :246-252

[4] INHIBITION OF CHOLESTEROL-SYNTHESIS INVITRO AND INVIVO BY ML-236A AND ML-236B, COMPETITIVE INHIBITORS OF 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE [J].

ENDO, A ;

TSUJITA, Y ;

KURODA, M ;

TANZAWA, K .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1977, 77 (01) :31-36

[5] Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy [J].

Hamacher-Brady, A. ;

Brady, N. R. ;

Logue, S. E. ;

Sayen, M. R. ;

Jinno, M. ;

Kirshenbaum, L. A. ;

Gottlieb, R. A. ;

Gustafsson, A. B. .

CELL DEATH AND DIFFERENTIATION, 2007, 14 (01) :146-157

[6] The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity [J].

Hanai, Jun-ichi ;

Cao, Peirang ;

Tanksale, Preeti ;

Imamura, Shintaro ;

Koshimizu, Eriko ;

Zhao, Jinghui ;

Kishi, Shuji ;

Yamashita, Michiaki ;

Phillips, Paul S. ;

Sukhatme, Vilkas P. ;

Lecker, Stewart H. .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (12) :3940-3951

[7] Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone [J].

Johnson, TE ;

Zhang, XH ;

Bleicher, KB ;

Dysart, G ;

Loughlin, AF ;

Schaefer, WH ;

Umbenhauer, DR .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2004, 200 (03) :237-250

[8] LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation [J].

Kabeya, Y ;

Mizushima, N ;

Yamamoto, A ;

Oshitani-Okamoto, S ;

Ohsumi, Y ;

Yoshimori, T .

JOURNAL OF CELL SCIENCE, 2004, 117 (13) :2805-2812

[9] Toxicity of statins on rat skeletal muscle mitochondria [J].

Kaufmann, P. ;

Toeroek, M. ;

Zahno, A. ;

Waldhauser, K. M. ;

Brecht, K. ;

Kraehenbuehl, S. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (19-20) :2415-2425

[10] Preventive effects of bicarbonate on cerivastatin-induced apoptosis [J].

Kobayashi, Masaki ;

Kaido, Fumie ;

Kagawa, Toshiki ;

Itagaki, Shirou ;

Hirano, Takeshi ;

Iseki, Ken .

INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2007, 341 (1-2) :181-188

← 1 2 3 →