Bezafibrate induces myotoxicity in human rhabdomyosarcoma cells via peroxisome proliferator-activated receptor α signaling
作者： Yan Zhao , Manabu Okuyama , Hiroyuki Hashimoto , Yoshiaki Tagawa , Takahito Jomori
DOI: 10.1016/J.TIV.2009.08.001
关键词:
摘要: Fibrates, the ligands of peroxisome proliferator-activated receptor alpha (PPARalpha), are used as a class lipid-lowering drugs in clinical practice for treatment dyslipidemia. Fibrates well tolerated most cases concomitantly with occasional adverse reactions including muscular toxicity, which is enhanced by combination statins. This study was designed to investigate effects bezafibrate PPARalpha agonist on human embryo rhabdomyosarcoma (RD) cells and possible mechanisms responsible bezafibrate-mediated myopathy. The results revealed that caused dose-dependent decrease cell viability, fortified association atorvastatin at pharmacological dose. Bezafibrate toxic doses 300 1000microM upregulated mRNA level, counteracted antagonist (MK886). dose induced typical apoptotic characteristics related inhibition phosphorylation Akt blocked antagonist. Toxic initiated significant increase pyruvate dehydrogenase kinase 4 protein levels, compromised MK886. These suggest critical roles signaling bezafibrate-induced myotoxicity involvement apoptosis through pathway.
elsevier.com
sci-hub.se 参考文章(41)
Daria Orszulak-Michalak, Magdalena Jasinska, Jacek Owczarek, Drug-induced myopathies. An overview of the possible mechanisms. Pharmacological Reports. ,vol. 57, pp. 23- 34 ,(2005)
Alan N Baer, Robert L Wortmann, Myotoxicity associated with lipid-lowering drugs. Current Opinion in Rheumatology. ,vol. 19, pp. 67- 73 ,(2007) , 10.1097/BOR.0B013E328010C559
Sumio Matzno, Keiko Tazuya-Murayama, Hiromi Tanaka, Shinya Yasuda, Motohiro Mishima, Takahiro Uchida, Toshikatsu Nakabayashi, Kenji Matsuyama, Evaluation of the synergistic adverse effects of concomitant therapy with statins and fibrates on rhabdomyolysis. Journal of Pharmacy and Pharmacology. ,vol. 55, pp. 795- 802 ,(2010) , 10.1211/002235703765951401
Sumio Matzno, Shinya Yasuda, Yuka Kitada, Takeshi Akiyoshi, Naoko Tanaka, Sachiko Juman, Kazumasa Shinozuka, Toshikatsu Nakabayashi, Kenji Matsuyama, Clofibrate-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation. Life Sciences. ,vol. 78, pp. 1892- 1899 ,(2006) , 10.1016/J.LFS.2005.08.003
Timothy E. Johnson, Xiaohua Zhang, Shu Shi, Diane R. Umbenhauer, Statins and PPARα agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment Toxicology and Applied Pharmacology. ,vol. 208, pp. 210- 221 ,(2005) , 10.1016/J.TAAP.2005.03.004
Takayoshi Maiguma, Koji Fujisaki, Yoshinori Itoh, Kazutaka Makino, Daisuke Teshima, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri, Ryozo Oishi, Cell-specific toxicity of fibrates in human embryonal rhabdomyosarcoma cells Naunyn-schmiedebergs Archives of Pharmacology. ,vol. 367, pp. 289- 296 ,(2003) , 10.1007/S00210-002-0660-9
T. Kubota, T. Yano, K. Fujisaki, Y. Itoh, R. Oishi, Fenofibrate induces apoptotic injury in cultured human hepatocytes by inhibiting phosphorylation of Akt. Apoptosis. ,vol. 10, pp. 349- 358 ,(2005) , 10.1007/S10495-005-0809-3
Béatrice Desvergne, Walter Wahli, Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine Reviews. ,vol. 20, pp. 649- 688 ,(1999) , 10.1210/EDRV.20.5.0380
Kamel M. Sharobeem, Brendan P. Madden, Russell Millner, Lindsey M. Rolfe, Carol A. Seymour, John Parker, Acute renal failure after cardiopulmonary bypass: a possible association with drugs of the fibrate group. Journal of Cardiovascular Pharmacology and Therapeutics. ,vol. 5, pp. 33- 39 ,(2000) , 10.1177/107424840000500105
Thomas F Franke, Christoph P Hornik, Lisa Segev, Grigoriy A Shostak, Chizuru Sugimoto, PI3K/Akt and apoptosis: size matters. Oncogene. ,vol. 22, pp. 8983- 8998 ,(2003) , 10.1038/SJ.ONC.1207115