Upregulation of IGF‐IIRα intensifies doxorubicin‐induced cardiac damage
| العنوان: | Upregulation of IGF‐IIRα intensifies doxorubicin‐induced cardiac damage |
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| المؤلفون: | Sudhir Pandey, Wei‐Wen Kuo, Tsung‐Jung Ho, Yu‐Lan Yeh, Chia‐Yao Shen, Ray‐Jade Chen, Ruey‐Lin Chang, Pei‐Ying Pai, V. Vijaya Padma, Chih‐Yang Huang |
| المصدر: | Journal of Cellular Biochemistry. 120:16956-16966 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Heart Defects, Congenital, 0301 basic medicine, p38 mitogen-activated protein kinases, Cardiomyopathy, Estrogen receptor, Apoptosis, Cardiomegaly, Biochemistry, Receptor, IGF Type 2, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Growth factor receptor, Atrial natriuretic peptide, medicine, Animals, Estrogen Receptor beta, Myocytes, Cardiac, Doxorubicin, Molecular Biology, Cardiotoxicity, Antibiotics, Antineoplastic, Chemistry, Estrogen Receptor alpha, Heart, Cell Biology, medicine.disease, Rats, Oxidative Stress, 030104 developmental biology, 030220 oncology & carcinogenesis, cardiovascular system, Cancer research, Rats, Transgenic, Cardiomyopathies, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt, Signal Transduction, medicine.drug |
| الوصف: | Cardiotoxicity by doxorubicin hampers its therapeutic potential as an anticancer drug, but mechanisms leading to cardiotoxicity remain contentious. Through this study, the functional contribution of insulin-like growth factor receptor type II α (IGF-IIRα) which is a novel stress-inducible protein was explored in doxorubicin-induced cardiac stress. Employing both in vitro H9c2 cells and in vivo transgenic rat models (SD-TG [IGF-IIRα]) overexpressing IGF-IIRα specifically in heart, we found that IGF-IIRα leads to cardiac structural abnormalities and functional perturbations that were severely aggravated by doxorubicin-induced cardiac stress. Overexpression of IGF-IIRα leads to cumulative elevation of stress associated cardiac hypertrophy and apoptosis factors. There was a significant reduction of survival associated proteins p-Akt and estrogen receptor β/α, and abnormal elevation of cardiac hypertrophy markers such as atrial natriuretic peptide, cardiac troponin-I, and apoptosis-inducing agents such as p53, Bax, and cytochrome C, respectively. IGF-IIRα also altered the expressions of AT1R, ERK1/2, and p38 proteins. Besides, IGF-IIRα also increased the reactive oxygen species production in H9c2 cells which were markedly aggravated by doxorubicin treatment. Together, we showed that IGF-IIRα is a novel stress-induced protein that perturbed cardiac homeostasis and cumulatively exacerbated the doxorubicin-induced cardiac injury that perturbed heart functions and ensuing cardiomyopathy. |
| تدمد: | 1097-4644 0730-2312 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::17f50700fc96179371d4c37e7d40df89 https://doi.org/10.1002/jcb.28957 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....17f50700fc96179371d4c37e7d40df89 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974644 07302312 |
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