scholarly journals Dexmedetomidine Protects against Myocardial Ischemia/Reperfusion Injury by Ameliorating Oxidative Stress and Cell Apoptosis through the Trx1-Dependent Akt Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Zhi-lin Wu ◽  
Jacques Robert Jeppe Davis ◽  
Yi Zhu
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Akt Pathway ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion ◽  
Isolated Rat

Dexmedetomidine (Dex) was reported to reduce oxidative stress and protect against myocardial Ischemia/Reperfusion (I/R) injury. However, the molecular mechanism involved in its antioxidant property is not fully elucidated. The present study was aimed at investigating whether the Trx1/Akt pathway participated in the cardioprotective effect of Dex. In the present study, I/R-induced myocardial injury in isolated rat hearts and OGD/R-induced injury in H9c2 cardiomyocytes were established. Our findings suggested that Dex ameliorated myocardial I/R injury by improving cardiac function, reducing myocardial apoptosis and oxidative stress, which was manifested by increased GSH and SOD contents, decreased ROS level, and MDA generation in both the isolated rat hearts and OGD/R-treated H9C2 cells. More importantly, it was found that the level of Trx1 was preserved, and Akt phosphorylation was significantly upregulated by Dex treatment. However, these effects of Dex were abolished by PX-12 (a specific Trx1 inhibitor) administration. Taken together, this study suggests that Dex plays a protective role in myocardial I/R injury, improves cardiac function, and relieves oxidative stress and cell apoptosis. Furthermore, our results present a novel signaling mechanism that the cardioprotective effect of Dex is at least partly achieved through the Trx1-dependent Akt pathway.

Endoxin-mediated myocardial ischemia reperfusion injury in rats in vitro

2004 ◽  
Vol 82 (6) ◽  
pp. 402-408 ◽  
Author(s):  
Yong-Sheng Ke ◽  
He-Gui Wang ◽  
De-Guo Wang ◽  
Gen-Bao Zhang
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Isolated Rat

Myocardial ischemia reperfusion results in an increase in intracellular sodium concentration, which secondarily increases intracellular calcium via Na+-Ca2+ exchange, resulting in cellular injury. Endoxin is an endogenous medium of digitalis receptor and can remarkably inhibit Na+/K+-ATPase activity. Although the level of plasma endoxin is significantly higher during myocardial ischemia, its practical significance is unclear. This research is to investigate whether endoxin is one of important factors involved in myocardial ischemia reperfusion injury. Ischemia reperfusion injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts. Heart rate (HR), left ventricular developed pressure (LVDP), and its first derivative (±dp/dtmax) were recorded. The endoxin contents, intramitochondrial Ca2+ contents, and the Na+/K+-ATPase activity in myocardial tissues were measured. Myocardial damages were evaluated by electron microscopy. The endoxin and intramitochondrial Ca2+ contents in myocardial tissues were remarkably higher, myocardial membrane ATPase activity was remarkably lower, the cardiac function was significantly deteriorated, and myocardial morphological damages were severe in myocardial ischemia reperfusion group vs. control. Anti-digoxin antiserum (10, 30 mg/kg) caused a significant improvement in cardiac function (LVDP and ±dp/dtmax), Na+/K+-ATPase activity, and myocardial morphology, and caused a reduction of endoxin and intramitochondrial Ca2+ contents in myocardial tissues. In the present study, the endoxin antagonist, anti-digoxin antiserum, protected the myocardium against the damages induced by ischemia reperfusion in isolated rat hearts. The results suggest that endoxin might be one of main factors mediating myocardial ischemia reperfusion injury.Key words: endoxin, anti-digoxin antiserum, myocardial reperfusion injury, morphological evaluation, Na+/K+-exchanging ATPase.

scholarly journals Transient Acidosis during Early Reperfusion Attenuates Myocardium Ischemia Reperfusion Injury via PI3k-Akt-eNOS Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Xin Qiao ◽  
Jinjin Xu ◽  
Qing-Jun Yang ◽  
Yun Du ◽  
Shaoqing Lei ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Early Reperfusion ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Myocardium Ischemia Reperfusion ◽  
Isolated Rat

In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway.

scholarly journals Mechanism of N-acetylcysteine in alleviating diabetic myocardial ischemia reperfusion injury by regulating PTEN/Akt pathway through promoting DJ-1

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Wenyuan Li ◽  
Wei Li ◽  
Yan Leng ◽  
Yonghong Xiong ◽  
Rui Xue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Akt Pathway ◽  
Myocardial Cells ◽  
Stress Injury ◽  
Apoptosis Rate ◽  
Oxidative Stress Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Ischemic heart disease is the main cardiovascular complication of diabetes patients which is mainly caused by oxidative stress. DJ-1 is the key regulator for myocardial protection through inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and activating Akt (also known as PKB or protein kinase B). This research is to investigate whether the antioxidant N-acetylcysteine (NAC) could alleviate diabetic myocardial ischemia/reperfusion (I/R) injury by the protective molecule DJ-1. DJ-1 in rat myocardial H9c2 cells and cardiac tissue was respectively knocked down by siRNA and adeno-associated virus (AAV). From the present study, it could be found that compared with high glucose (HG)-normal (N)/DM group, hypoxia/reoxygenation (H/R) or I/R injury can aggravate oxidative stress injury and apoptosis rate of myocardial cells, inhibit the expression of Bcl-2, activate the BAX and cleaved caspase-3 (c-caspase-3) protein and PTEN/Akt pathway. However, in the groups of HG-N, DM, HG-N+I/R and DM+I/R, NAC can significantly reduce oxidative stress injury and apoptosis rate of myocytes, promote the Bcl-2 and DJ-1 molecules, inhibit BAX and c-caspase-3 protein and PTEN/Akt pathway. Compared with HG-N+I/R+NAC and DM+I/R+NAC groups, the oxidative stress injury, apoptosis rate of myocardial cells and heart tissues increased after the knockdown of DJ-1, the expression of Bcl-2 and DJ-1 were inhibited, the BAX and c-caspase-3 expression was increased, and PTEN/Akt pathway was activated. Taken together, the findings suggest that NAC can reduce I/R injury in diabetic myocardium by up-regulating the PTEN/Akt pathway through the level of DJ-1.

scholarly journals Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling

2018 ◽  
Vol 47 (3) ◽  
pp. 1193-1206 ◽  
Author(s):  
Yunyang Lu ◽  
Yingda Feng ◽  
Dan Liu ◽  
Zhiran Zhang ◽  
Kai Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardioprotective Effect ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Production Of Hydrogen ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Myocardial ischemia/reperfusion (MI/R) injury is a leading factor responsible for damage in myocardial infarction, resulting in additional injury to cardiac tissues involved in oxidative stress, inflammation, and apoptosis. Thymoquinone (TQ), the main constituent of Nigella sativa L. seeds, has been reported to possess various biological activities. However, few reports regarding myocardial protection are available at present. Therefore, this study was conducted aiming to investigate the protective effect of TQ against MI/R injury and to clarify its potential mechanism. Methods: MI/R injury models of isolated rat hearts and neonatal rat cardiomyocytes were established. The Langendorff isolated perfused heart system, triphenyltetrazolium chloride staining, gene transfection, TransLaser scanning confocal microscopy, and western blotting were employed to evaluate the cardioprotection effect of TQ against MI/R injury. Results: Compared with the MI/R group, TQ treatment could remarkably improve left ventricular function, decrease myocardial infarct size and production of lactate dehydrogenase (LDH), and attenuate mitochondrial oxidative damage by elevating superoxide dismutase (SOD) activity and reducing production of hydrogen peroxide (H2O2) and malonaldehyde (MDA). Moreover, the cardioprotective effect of TQ was accompanied by up-regulated expression of SIRT1 and inhibition of p53 acetylation. Additionally, TQ treatment could also enhance mitochondrial function and reduce the number of apoptotic cardiomyocytes. Nonetheless, the cardioprotective effect of TQ could be mitigated by SIRT1 inhibitor sirtinol and SIRT1 siRNA, respectively, which was achieved through inhibition of the SIRT1 signaling pathway. Conclusions: The findings in this study demonstrate that TQ is efficient in attenuating MI/R injury through activation of the SIRT1 signaling pathway, which can thus reduce mitochondrial oxidative stress damage and cardiomyocyte apoptosis.

scholarly journals LncRNA LINC00461 exacerbates myocardial ischemia-reperfusion injury via microRNA-185-3p/Myd88

2021 ◽  
Author(s):  
Feng Gao ◽  
Xiaochen Wang ◽  
Tingting Fan ◽  
Zhidan Luo ◽  
Mengqin Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Primary Response ◽  
Cardiomyocyte Apoptosis ◽  
Non Coding Rna ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Objective Long non-coding RNA (lncRNA) play critically in myocardial ischemia-reperfusion (I/R) injury. Thus, it was proposed to investigate the mechanism of LINC00461 in the disease through mediating microRNA-185-3p (miR-185-3p)/myeloid differentiation primary response gene 88 (Myd88) axis. Methods Mice with I/R injury were injected with the vectors that altered miR-185-3p and LINC00461 expression. miR-185-3p, LINC00461 and Myd88 expression in mice with I/R injury were measured, as well as cardiac function, hemodynamics, myocardial fibrosis, infarction area, oxidative stress, and cardiomyocyte apoptosis. Results Raised LINC00461 and Myd88 and suppressed miR-185-3p levels were measured in I/R mice. Down-regulating LINC00461 or up-regulating miR-185-3p recovered cardiac function, reduced myocardial collagen hyperplasia, fibrosis and infarction, and attenuated oxidative stress and cardiomyocyte apoptosis in mice with I/R. Conclusion Down-regulation of LINC00461 attenuates myocardial I/R injury via suppressing miR-185-3p-targeted Myd88 expression.

Activation of proteolytic enzymes and depression of the sarcolemmal Na+/K+-ATPase in ischemia–reperfused heart may be mediated through oxidative stress

2012 ◽  
Vol 90 (2) ◽  
pp. 249-260 ◽  
Author(s):  
Raja B. Singh ◽  
Larry Hryshko ◽  
Darren Freed ◽  
Naranjan S. Dhalla
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Proteolytic Enzymes ◽  
Ischemia Reperfusion ◽  
The Other ◽  
Calpain Activity ◽  
Rat Hearts ◽  
Induced Changes ◽  
Isolated Rat

We tested whether the activation of proteolytic enzymes, calpain, and matrix metalloproteinases (MMPs) during ischemia–reperfusion (I/R) is mediated through oxidative stress. For this purpose, isolated rat hearts were subjected to a 30 min global ischemia followed by a 30 min reperfusion. Cardiac function was monitored and the activities of Na+/K+-ATPase, Mg2+-ATPase, calpain, and MMP were measured. Depression of cardiac function and Na+/K+-ATPase activity in I/R hearts was associated with increased calpain and MMP activities. These alterations owing to I/R were similar to those observed in hearts perfused with hypoxic medium, H2O2 and xanthine plus xanthine oxidase. The I/R-induced changes were attenuated by ischemic preconditioning as well as by perfusing the hearts with N-acetylcysteine or mercaptopropionylglycine. Inhibition of MMP activity in hearts treated with doxycycline depressed the I/R-induced changes in cardiac function and Na+/K+-ATPase activity without affecting the calpain activation. On the other hand, inhibition of calpain activity upon treatment with leupeptin or MDL 28170 significantly reduced the MMP activity in addition to attenuating the I/R-induced alterations in cardiac function and Na+/K+-ATPase activity. These results suggest that the I/R-induced depression in Na+/K+-ATPase and cardiac function may be a consequence of the increased activities of both calpain and MMP because of oxidative stress in the heart.

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