Exendin-4 Protects against Hyperglycemia-Induced Cardiomyocyte Pyroptosis via the AMPK-TXNIP Pathway
المؤلفون المشاركون
Wei, Hong
Bu, Rui
Yang, Qinghui
Jia, Jing
Li, Tao
Wang, Qiuping
Chen, Yanjun
المصدر
العدد
المجلد 2019، العدد 2019 (31 ديسمبر/كانون الأول 2019)، ص ص. 1-13، 13ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2019-12-09
دولة النشر
مصر
عدد الصفحات
13
التخصصات الرئيسية
الملخص EN
Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which results in cardiac hypertrophy and subsequent heart failure.
Chronic inflammation in the diabetic heart results in loss of cardiomyocytes and subsequentially cardiac dysfunction.
Accumulated evidence implicated pyroptosis as a vital contributor to the hyperglycemia-induced cardiac inflammatory response.
Exendin-4, a GLP analog, promotes survival of cardiomyocytes in cardiovascular diseases, including diabetic cardiomyopathy.
However, the role of Exendin-4 in cardiac pyroptosis remains to be elucidated.
Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats.
The activity of caspase-1 and production of pyroptotic cytokines were significantly inhibited by Exendin-4 treatment in the diabetic heart and in high glucose-treated cardiomyocytes as well.
In an effort to understand the signaling mechanisms underlying the antipyroptotic property of Exendin-4, we found that blockade of AMPK, an oxidative stress sensor, activity diminished the antipyroptotic property of Exendin-4.
Phosphorylation of AMPK resulted in degeneration of TXNIP that promoted the activation of the NLRP3 inflammasome.
Exendin-4 treatment decreased the protein level of TXNIP.
Moreover, RNA silencing of TXNIP mimicked the antipyroptotic actions of Exendin-4.
These findings promoted us to propose a new signaling pathway mediating cardioprotective effect of Exendin-4 under hyperglycemic conditions: Exendin-4 → ROS↓ → pAMPK↑ → TXNIP↓ → caspase-1↓ → IL-1β and IL-18↓ → pyroptosis↓.
In general, our study identified Exendin-4 as a pyroptotic inhibitor protecting against hyperglycemia-induced cardiomyocyte pyroptosis via the AMPK-TXNIP pathway.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Wei, Hong& Bu, Rui& Yang, Qinghui& Jia, Jing& Li, Tao& Wang, Qiuping…[et al.]. 2019. Exendin-4 Protects against Hyperglycemia-Induced Cardiomyocyte Pyroptosis via the AMPK-TXNIP Pathway. Journal of Diabetes Research،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1173348
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Wei, Hong…[et al.]. Exendin-4 Protects against Hyperglycemia-Induced Cardiomyocyte Pyroptosis via the AMPK-TXNIP Pathway. Journal of Diabetes Research No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1173348
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Wei, Hong& Bu, Rui& Yang, Qinghui& Jia, Jing& Li, Tao& Wang, Qiuping…[et al.]. Exendin-4 Protects against Hyperglycemia-Induced Cardiomyocyte Pyroptosis via the AMPK-TXNIP Pathway. Journal of Diabetes Research. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1173348
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1173348
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