Adenosine 2 receptor regulates autophagy and apoptosis to alleviate ischemia reperfusion injury in type 2 diabetes via IRE-1 signaling.

Autor: Yacouba Moukeila MB; Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China., Thokerunga E; Program and Department of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China., He F; Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China., Bongolo CC; Program and Department of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China., Xia Y; Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China., Wang F; Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China., Gado AF; Department of Anesthesia and Intensive Care, Hôpital Général de Référence Niamey, Niamey, Niger., Mamoudou H; Department of Anesthesia and Intensive Care, National Hospital of Niamey, Niamey, Niger., Khan S; Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China., Ousseina B; Department of Cardiovascular and Internal Medicine, Niamey Amirou Boubacar Diallo National Hospital, Abdou Moumouni University, Niamey, Niger., Ousmane HA; Department of Anesthesia and Intensive Care, Hôpital Général de Référence Niamey, Niamey, Niger., Diarra D; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China., Ke J; Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. 1219628972@qq.com., Zhang Z; Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. zhangzz@whu.edu.cn., Wang Y; Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. wyl0342@sina.com.
Jazyk: angličtina
Zdroj: BMC cardiovascular disorders [BMC Cardiovasc Disord] 2023 Mar 24; Vol. 23 (1), pp. 154. Date of Electronic Publication: 2023 Mar 24.
DOI: 10.1186/s12872-023-03116-y
Abstrakt: Purpose: This study aimed to determine the effect and mechanism of action of adenosine 2 receptor (A2R) activation on myocardial ischemia reperfusion injury (MIRI) under diabetic conditions.
Methods: MIRI type 2 diabetic rats and H9C2 cardiomyocytes were treated with A2R agonist and then subjected to hypoxia for 6 h and reoxygenation for 18 h. Myocardial damage, and infarct size were determined by cardiac ultrasound. Indicators of cardiomyocyte injury, creatine kinase-MB and cardiac troponin I were detected by Enzyme Linked Immunosorbent Assay. Endoplasmic reticulum stress (ERS) was determined through measuring the expression levels of ERS related genes GRP78, p-IRE1/IRE1, and p-JNKJNK. The mechanism of A2R cardio protection in MIRI through regulating ERS induced autophagy was determined by investigating the ER resident protein IRE-1. The ER-stress inducer Tunicamycin, and the IRE-1 inhibitor STF in combination with the A2R agonist NECA were used, and the cellular responses were assessed through autophagy proteins expression Beclin-1, p62, LC3 and apoptosis.
Results: NECA improved left ventricular function post MIRI, limited myocardial infarct size, reduced myocardial damage, decreased cardiomyocytes apoptosis, and attenuated ERS induced autophagy through regulating the IRE-XBP1s-CHOP pathway. These actions resulted into overall protection of the myocardium against MIRI.
Conclusion: In summary, A2R activation by NECA prior to ischemia attenuates apoptosis, reduces ERS induced autophagy and restores left ventricular function. This protective effect occurs through regulating the IRE1-XBPs-CHOP related mechanisms. NECA is thus a potential target for the treatment of MIRI in patient with type 2 diabetes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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