Insulin-like growth factor II receptor-α is a novel stress-inducible contributor to cardiac damage underpinning doxorubicin-induced oxidative stress and perturbed mitochondrial autophagy

ASIA unversity > 醫學暨健康學院 > 醫學檢驗暨生物技術學系 > 期刊論文 > Item 310904400/112708

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/112708

题名:	Insulin-like growth factor II receptor-α is a novel stress-inducible contributor to cardiac damage underpinning doxorubicin-induced oxidative stress and perturbed mitochondrial autophagy
作者:	Pande, Sudhir;Pandey, Sudhir;Kuo, Wei-Wen;Kuo, Wei-Wen;She, Chia-Yao;Shen, Chia-Yao;Yeh, Yu-Lan;Yeh, Yu-Lan;Tsung-Jung, H;Ho, Tsung-Jung;Che, Ray-Jade;Chen, Ray-Jade;Cha, Ruey-Lin;Chang, Ruey-Lin;Pai, Pei-Ying;Pai, Pei-Ying;Padma, Vijaya;Viswanadha, Vijaya Padma;Hu, Chih-Yang;Huang, Chih-Yang;黃志揚;Huang, Chih-Yang
贡献者:	醫學檢驗暨生物技術學系
关键词:	IGF-IIRα;cardiotoxicity;doxorubicin;mitophagy;transgenic rats.
日期:	2019-09
上传时间:	2020-08-20 07:10:44 (UTC+0)
出版者:	亞洲大學
摘要:	Doxorubicin (DOX) is an anthracycline antibiotic commonly employed for the treatment of various cancers. However, its therapeutic uses are hampered by side effects associated with cumulative doses during the course of treatment. Whereas deregulation of autophagy in the myocardium has been involved in a variety of cardiovascular diseases, the role of autophagy in DOX-induced cardiomyopathy remains debated. Our earlier studies have shown that DOX treatment in a rat animal model leads to increased expression of the novel stress-inducible protein insulin-like growth factor II receptor-α (IGF-IIRα) in cardiac tissues, which exacerbated the cardiac injury by enhancing oxidative stress and p53-mediated mitochondria-dependent cardiac apoptosis. Through this study, we investigated the contribution of IGF-IIRα to dysregulation of autophagy in heart using both in vitro H9c2 cells (DOX treated, 1 µM) and in vivo transgenic rat models (DOX treated, 5 mg/kg ip for 6 wk) overexpressing IGF-IIRα specifically in the heart. We found that IGF-IIRα primarily localized to mitochondria, causing increased mitochondrial oxidative stress that was severely aggravated by DOX treatment. This was accompanied by a significant perturbation in mitochondrial membrane potential and increased leakage of cytochrome c, causing increased cleaved caspase-3 activity. There were significant alterations in phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated Unc-51 like kinase-1 (p-ULK1), PARKIN, PTEN-induced kinase 1 (PINK1), microtubule-associated protein 1 light chain 3 (LC3), and p62 proteins, which were more severely disrupted under the combined effect of IGF-IIRα overexpression plus DOX. Finally, LysoTracker Red staining showed that IGF-IIRα overexpression causes lysosomal impairment, which was rescued by rapamycin treatment. Taken together, we found that IGF-IIRα leads to mitochondrial oxidative stress, decreased antioxidant levels, disrupted mitochondrial membrane potential, and perturbed mitochondrial autophagy contributing to DOX-induced cardiomyopathy.
關聯:	AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
显示于类别:	[醫學檢驗暨生物技術學系] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	200	检视/开启

检视Licence

在ASIAIR中所有的数据项都受到原著作权保护.

数据加载中.....