Alterations in Dystrophin-Related Glycoproteins in Development of Right Ventricular Failure in Rats

Journal of Pharmacological Sciences

Suguru Kojima¹  Satoshi Takeo¹  Norio Takagi¹  Takuya Daicho¹  Saori Takano¹  Yoriko Daisho¹  Kouichi Tanonaka¹  Yugo Tejima¹  Tetsuro Marunouchi¹ 

[1] Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, Japan

关键词: dystrophin-related glycoprotein;    right ventricular failure;    calpain;    matrix metalloproteinase;    monocrotaline;   

DOI  :  10.1254/jphs.09208FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(2)Genetic depletion of the dystrophin-related glycoprotein (DRGP) complex causes cardiomyopathy in animals and humans. The present study was undertaken to explore the possible involvement of alterations in DRGP in the development of the right ventricular failure in monocrotaline-administered rats (MCT rats). At the 6th and 8th weeks after subcutaneous administration of 60 mg/kg monocrotaline, echocardiographic examination showed that cardiac output indices were decreased and that the right ventricular Tei indices were increased, suggesting that right ventricular failure occurs, at the latest, by 6 weeks after monocrotaline-administration. The levels of α- and β-sarcoglycan and β-dystroglycan in the right ventricle of the MCT rats at the 6th and 8th weeks were markedly decreased, and these decreases were inversely related to the increase in the right ventricular Tei index of the MCT-administered animals. The content and activity of the Ca2+-activated neutral protease m-calpain in the right ventricle of the MCT rats were increased at the 4th to 8th weeks and those of matrix metalloproteinase-2, at the 6th and 8th weeks. These results suggest that m-calpain– and/or matrix metalloproteinase-2–mediated alterations in the contents of α-sarcoglycan, β-sarcoglycan, and β-dystroglycan may be involved in the development of right ventricular failure in MCT rats.

【 授权许可】

Unknown