Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes
المؤلفون المشاركون
Wang, Meihui
Lin, Jun
Lv, Qingbo
Wang, Jiacheng
Xue, Zhimin
Hua, Chunting
Shen, Zhida
Song, Yinjing
Ying, Hangying
Zhou, Binquan
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-15، 15ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-11-27
دولة النشر
مصر
عدد الصفحات
15
التخصصات الرئيسية
الملخص EN
Background.
Coronary heart disease is currently the leading cause of death in humans.
Its poor prognosis and high mortality are associated with myocardial ischemia, which leads to metabolic disorder-related cardiomyocyte apoptosis and reactive oxygen species (ROS) production.
Previous cardiovascular metabolomics studies in humans and mice have shown that proline metabolism is severely altered after cardiomyocyte hypoxia.
Proline dehydrogenase (PRODH) is located on the inner mitochondrial membrane and is an enzyme that catalyzes the first step of proline catabolism, which plays an important role in improving the cellular redox state.
In vitro oxygen-glucose deprivation can mimic in vivo myocardial ischemic injury.
This study is aimed at investigating whether enhancing proline metabolism by overexpressing PRODH can ameliorate hypoxia-induced injury in cardiomyocytes and to reveal the related altered metabolites and mechanistic pathway via untargeted metabolomics analysis.
Methods and Results.
First, through public database analysis and RT-qPCR and western blot analyses in a cardiomyocyte hypoxia model, we found that the expression of the proline-degrading enzyme PRODH was downregulated after myocardial infarction and hypoxia exposure.
Second, LDH assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), DHE staining, flow cytometric apoptosis analysis with DCFH and Annexin V-FITC/PI, and western blot analysis were used to assess the injury level in cardiomyocytes.
Enhanced proline metabolism induced by PRODH overexpression reduced the levels of reactive oxidative stress and apoptosis, whereas PRODH knockdown had the opposite effects.
Third, untargeted metabolomics analysis revealed that the protective effect was associated with significant changes in metabolism linked to sphingolipid signaling pathways, unsaturated fatty acid biosynthesis, phosphocreatine, glutathione disulfide, aminoacyl-tRNA biosynthesis, and ABC transporters.
Conclusions.
Our study demonstrated a protective effect of enhanced proline metabolism in cardiomyocytes under hypoxia, providing a novel strategy for exploring new treatments for coronary heart disease.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Wang, Jiacheng& Xue, Zhimin& Hua, Chunting& Lin, Jun& Shen, Zhida& Song, Yinjing…[et al.]. 2020. Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1205816
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Wang, Jiacheng…[et al.]. Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-15.
https://search.emarefa.net/detail/BIM-1205816
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Wang, Jiacheng& Xue, Zhimin& Hua, Chunting& Lin, Jun& Shen, Zhida& Song, Yinjing…[et al.]. Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1205816
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1205816
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر