Selenium incorporated guar gum nanoparticles safeguard mitochondrial bioenergetics during ischemia reperfusion injury in H9c2 cardiac cells

Mitochondria play a fundamental role in the energetics of cardiac cells. Moreover, mitochondria are involved in cardiac ischemia/reperfusion injury by opening the mitochondrial permeability transition pore which is the major cause of cell death. The preservation of mitochondrial function is an essential component of the cardioprotective mechanism. The involvement of mitochondrial K+ transport in this complex phenomenon seems to be well established. Several mitochondrial K+ channels in the inner mitochondrial membrane, such as ATP-sensitive, voltage-regulated, calcium-activated and Na+-activated channels, have been discovered. This obliges us to ask the following question: why is the simple potassium ion influx process carried out by several different mitochondrial potassium channels? In this review, we summarize the current knowledge of both the properties of mitochondrial potassium channels in cardiac mitochondria and the current understanding of their multidimensional functional role. We also critically summarize the pharmacological modulation of these proteins within the context of cardiac ischemia/reperfusion injury and cardioprotection.

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Intracardiac administration of ephrinA1-Fc preserves mitochondrial bioenergetics during acute ischemia/reperfusion injury

Life Sciences ◽

10.1016/j.lfs.2019.117053 ◽

2019 ◽

Vol 239 ◽

pp. 117053 ◽

Cited By ~ 3

Author(s):

Maria J. Torres ◽

Kelsey L. McLaughlin ◽

Randall H. Renegar ◽

Smrithi Valsaraj ◽

K'Shylah S. Whitehurst ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Acute Ischemia ◽

Mitochondrial Bioenergetics

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Amobarbital, high K + and lidocaine protect hearts against ischemia reperfusion injury by differential changes in mitochondrial bioenergetics

The FASEB Journal ◽

10.1096/fasebj.20.4.a319 ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Mohammed Aldakkak ◽

David F Stowe ◽

James S Heisner ◽

Edward J Lesnefsky ◽

Qun Chen ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mitochondrial Bioenergetics ◽

High K

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Low frequency electromagnetic field decreases ischemia–reperfusion injury of human cardiomyocytes and supports their metabolic function

Experimental Biology and Medicine ◽

10.1177/1535370218779773 ◽

2018 ◽

Vol 243 (10) ◽

pp. 809-816 ◽

Cited By ~ 2

Author(s):

Dariusz Biały ◽

Magdalena Wawrzyńska ◽

Iwona Bil-Lula ◽

Anna Krzywonos-Zawadzka ◽

Agnieszka Sapa-Wojciechowska ◽

...

Keyword(s):

Endothelial Cells ◽

Electromagnetic Field ◽

Reperfusion Injury ◽

Cardiac Myocytes ◽

Metabolic Activity ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Low Frequency ◽

Cardiac Cells ◽

Human Cardiomyocytes

Electromagnetic field at extremely low frequencies plays a significant role in the physiological function of human tissues and systems. It is shown that electromagnetic field inhibits production of reactive oxygen species which are involved in heart injury triggered by oxidative stress. We hypothesize that low frequency electromagnetic field protects function of cardiac cells from ischemia–reperfusion injury. Human cardiac myocytes, endothelial cells, and cardiac fibroblast underwent ischemia–reperfusion conditions in the presence or in the absence of low frequency electromagnetic field. LDH and MMP-2 activities (as markers of cell injury), and cell metabolic activity (by fluorescein diacetate staining) were measured to determine the protective role of low frequency electromagnetic field. Our data showed that short courses of low frequency electromagnetic field protect cardiac cells from cellular damage and preserve their metabolic activity during ischemia–reperfusion. This study demonstrates the possibility to use of low frequency electromagnetic field as strategy for the prevention or therapy of ischemia–reperfusion injury. Impact statement In our study, we showed that LF-EMF may be protective for heart during ischemia–reperfusion (I/R). Following is the short description of the main findings: (a) the response to the I/R injury was different for endothelial cells, fibroblasts, and cardiomyocytes; (b) I/R decreases MMP-2 activity in cardiac myocytes and fibroblasts; (c) I/R increases MMP-2 activity in endothelial cells; (d) LF-EMF reverses these changes; (e) LF-EMF protects cells from injury and preserves their metabolic activity.

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Abstract 255: Cardiac Ischemia and Reperfusion Injury: The Emerging Role of Sialidase Neu3

Circulation Research ◽

10.1161/res.127.suppl_1.255 ◽

2020 ◽

Vol 127 (Suppl_1) ◽

Author(s):

Marco Piccoli ◽

Maria Elena Canali ◽

Paola Rota ◽

Paolo La Rocca ◽

Andrea Ghiroldi ◽

...

Keyword(s):

Cell Proliferation ◽

Reperfusion Injury ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Cells ◽

Full Potential ◽

Ischemia And Reperfusion Injury ◽

Erk Activation

Reperfusion strategies, together with thrombolytic therapies, represent life-saving approaches to restore the blood flow in the cardiac tissue after acute myocardial infarction (AMI). However, they inevitably induce the so-called ischemia/reperfusion injury (IRI), resulting in increased cardiomyocytes damage and heart failure. In this context, many efforts have been made to clarify the molecular mechanisms involved in IRI, and the activation of pro-survival kinases, such as Akt and Erk, as well as of the hypoxia-inducible factor (HIF) has been recognized to be critical. Along this line, we discovered a novel mechanism of HIF-1α activation mediated by sialidase Neu3, which is PHDs independent, and that it increased muscle cells resistance to hypoxic stress, through the activation of Akt and Erk pathways. Moreover, an upregulation of Neu3 expression was observed under chronic hypoxia in cyanotic congenital cardiac patients.On these premises, this study aims at investigating the role of Neu3 in protecting cardiac cells against IRI. In particular, H9C2 rat cardiomyoblasts were exposed to an IRI model in vitro revealing a marked reduction in cell proliferation. This was accompanied by the modulation of Neu3 that was characterized by its progressive down-regulation during the ischemic phase, followed by its reactivation during reperfusion. These experiments resembled Neu3 modulation we observed in an IRI mouse model, obtained by the temporary occlusion of the LAD coronary vessel. Interestingly, overexpression of Neu3 significantly increased cardiomyoblasts resistance to IRI, both in terms of cell proliferation and resistance to apoptosis, as well as promoted HIF-1α and Akt/Erk activation. Remarkably, the treatment with Akt and Erk inhibitors completely reverted the beneficial effects mediated by Neu3 upregulation. Likewise, sialidase Neu3 inhibition reduced Akt/Erk activation, resulting in the complete loss of Neu3-mediated cardioprotection. In conclusion, our results demonstrate the role of sialidase Neu3 in counteracting the detrimental effects of IRI, calling for further studies to unveil its full potential as a therapeutic target to support current strategies to manage cardiac damage and to improve patients recover after AMI.

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MicroRNA miR-24-3p Reduces Apoptosis and Regulates Keap1-Nrf2 Pathway in Mouse Cardiomyocytes Responding to Ischemia/Reperfusion Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/7042105 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 21

Author(s):

Xu Xiao ◽

Zhigang Lu ◽

Victor Lin ◽

Adam May ◽

Daniel H. Shaw ◽

...

Keyword(s):

Reperfusion Injury ◽

Reporter Gene ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Cell ◽

Cardiac Cells ◽

Expression Level ◽

Luciferase Reporter ◽

Luciferase Reporter Gene

In recent years, microRNAs (miRNAs) have received increasing attention for their role in ischemia/reperfusion injury (I/RI), and many miRNAs have been demonstrated to play a very important role in cardiac I/RI. The miRNA miR-24-3p is a tumor suppressor that regulates multiple tumors; however, it remains unclear whether the expression level of miR-24-3p is altered in cardiac cells under I/RI. In this study, we used mouse primary cardiomyocytes and the H9C2 cardiomyocyte cell line to perform in vitro stimulated ischemia/reperfusion (SI/R) and then detected miR-24-3p expression level using quantitative real-time PCR (qRT-PCR). We discovered that the expression of miR-24-3p was significantly increased in cardiomyocytes following SI/R, and that the miR-24-3p level was inversely correlated to the ischemia marker HIF-1a. Furthermore, we transfected cardiomyocytes with miR-24-3p mimic or inhibitor to explore the role of miR-24-3p in cardiomyocyte ischemia/reperfusion injury in vitro. We performed flow cytometry to detect the apoptotic rate of H9C2 cardiomyocytes and found that the transfection of miR-24-3p mimic resulted in the decrease of the apoptosis rate of cardiomyocytes after SI/R, whereas the transfection of miR-24-3p inhibitor increased the number of apoptotic cardiomyocytes. These data suggest that the overexpression of miR-24-3p could reduce in vitro myocardial cell apoptosis induced by I/R injury. Finally, we applied the dual luciferase reporter gene system to verify whether miR-24-3p targets the Keap1 gene, and found that the luciferase signal intensity from a vector carrying the Keap1 wild-type reporter gene was significantly reduced after transfection with miR-24-3p mimic. The Keap1 protein level was also reduced following the transfection of miR-24-3p. The results from this study suggest a novel function of miR-24-3p in protecting cardiomyocytes from ischemia/reperfusion injury by the activation of the Nrf2-Keap1 pathway.

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Melatonin Attenuates Cardiac Ischemia-Reperfusion Injury through Modulation of IP3R-Mediated Mitochondria-ER Contact

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/1370862 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Wenya Li ◽

Botao Liu ◽

Lin Wang ◽

Jilie Liu ◽

Xiuhui Yang ◽

...

Keyword(s):

Reperfusion Injury ◽

Mitochondrial Permeability Transition ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Permeability Transition ◽

Cardiac Cells ◽

Mitochondrial Potential ◽

Rat Cardiomyocytes ◽

Postischemic Reperfusion

Although the interplay between mitochondria and ER has been identified as a crucial regulator of cellular homeostasis, the pathogenic impact of alterations in mitochondria-ER contact sites (MERCS) during myocardial postischemic reperfusion (I/R) injury remains incompletely understood. Therefore, in our study, we explored the beneficial role played by melatonin in protecting cardiomyocytes against reperfusion injury via stabilizing mitochondria-ER interaction. In vitro exposure of H9C2 rat cardiomyocytes to hypoxia/reoxygenation (H/R) augmented mitochondrial ROS synthesis, suppressed both mitochondrial potential and ATP generation, and increased the mitochondrial permeability transition pore (mPTP) opening rate. Furthermore, H/R exposure upregulated the protein content of CHOP and caspase-12, two markers of ER stress, and enhanced the transcription of main MERCS tethering proteins, namely, Fis1, BAP31, Mfn2, and IP3R. Interestingly, all the above changes could be attenuated or reversed by melatonin treatment. Suggesting that melatonin-induced cardioprotection works through normalization of mitochondria-ER interaction, overexpression of IP3R abolished the protective actions offered by melatonin on mitochondria-ER fitness. These results expand our knowledge on the cardioprotective actions of melatonin during myocardial postischemic reperfusion damage and suggest that novel, more effective treatments for acute myocardial reperfusion injury might be achieved through modulation of mitochondria-ER interaction in cardiac cells.

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