Mitochondrial and mitochondrial‐independent pathways of myocardial cell death during ischaemia and reperfusion injury

Cell death is an important component of the pathophysiology of any disease. Myocardial disease is no exception. Understanding how and why cells die, particularly in the heart where cardiomyocyte regeneration is limited at best, becomes a critical area of study. Ferroptosis is a recently described form of nonapoptotic cell death. It is an iron-mediated form of cell death that occurs because of accumulation of lipid peroxidation products. Reactive oxygen species and iron-mediated phospholipid peroxidation is a hallmark of ferroptosis. To date, ferroptosis has been shown to be involved in cell death associated with Alzheimer’s disease, Huntington’s disease, cancer, Parkinson’s disease, and kidney degradation. Myocardial reperfusion injury is characterized by iron deposition as well as reactive oxygen species production. These conditions, therefore, favor the induction of ferroptosis. Currently there is no available treatment for reperfusion injury, which accounts for up to 50% of the final infarct size. This review will summarize the evidence that ferroptosis can induce cardiomyocyte death following reperfusion injury and the potential for this knowledge to open new therapeutic approaches for myocardial ischemia-reperfusion injury.

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Cell cycle arrest and cell death correlate with the extent of ischaemia and reperfusion injury in patients following kidney transplantation - results of an observational pilot study

Transplant International ◽

10.1111/tri.13148 ◽

2018 ◽

Vol 31 (7) ◽

pp. 751-760 ◽

Cited By ~ 2

Author(s):

Felix C. F. Schmitt ◽

Eduardo Salgado ◽

Janina Friebe ◽

Thomas Schmoch ◽

Florian Uhle ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Kidney Transplantation ◽

Pilot Study ◽

Reperfusion Injury ◽

Cell Cycle Arrest ◽

Cycle Arrest ◽

Ischaemia And Reperfusion

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Na+ overload-induced mitochondrial damage in the ischemic heart

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y04-124 ◽

2004 ◽

Vol 82 (12) ◽

pp. 1033-1043 ◽

Cited By ~ 8

Author(s):

Satoshi Takeo ◽

Kouichi Tanonaka

Keyword(s):

Cell Death ◽

Free Radicals ◽

Reperfusion Injury ◽

Myocardial Contractility ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ion Homeostasis ◽

Myocardial Cell ◽

Myocardial Reperfusion ◽

Contractile Dysfunction

Ischemia induces a decrease in myocardial contractility that may lead more or less to contractile dysfunction in the heart. When the duration of ischemia is relatively short, myocardial contractility is immediately reversed to control levels upon reperfusion. In contrast, reperfusion induces myocardial cell death when the heart is exposed to a prolonged period of ischemia. This phenomenon is the so-called "reperfusion injury". Numerous investigators have reported the mechanisms underlying myocardial reperfusion injury such as generation of free radicals, disturbance in the intracellular ion homeostasis, and lack of energy for contraction. Despite a variety of investigations concerning the mechanisms for ischemia and ischemia–reperfusion injury, ionic disturbances have been proposed to play an important role in the genesis of the ischemia–reperfusion injury. In this present study, we focused on the contribution of Na+ overload and mitochondrial dysfunction during ischemia to the genesis of this ischemia–reperfusion injury.Key words: mitochondria, myocardial ischemia, Na+ channels, Na+/H+ exchanger, Na+ overload.

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Myocardial protection against reperfusion injury: The cGMP pathway

Thrombosis and Haemostasis ◽

10.1160/th08-11-0764 ◽

2009 ◽

Vol 101 (04) ◽

pp. 635-642 ◽

Cited By ~ 39

Author(s):

Luis Agulló ◽

Carmem Lluisa Sartorio ◽

Marisol Ruiz-Meana ◽

David Garcia-Dorado

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Endothelial Cells ◽

Cell Death ◽

Reperfusion Injury ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Myocardial Cell ◽

Cgmp Pathway ◽

Cgmp Synthesis

SummaryReperfusion injury may cause myocardial cell death and limit the benefit achieved by restoration of coronary artery patency in patients with acute myocardial infarction. The mechanism includes altered Ca2+ handling with cytosolic and mitochondrial Ca2+ overload, Ca2+- and ATP-dependent hypercontraction, cytoskeletal fragility, mitochondrial permeability transition and gap junction-mediated propagation of cell death, as well as alterations in non-cardiomyocyte cells, in particular platelets and endothelial cells. cGMP modulates favorably all these mechanism, mainly through PKG-mediated actions, but cGMP synthesis is altered in reperfused cardiomyocytes and endothelial cells by mechanisms that are only partially understood. Stimulation of cGMP synthesis during initial reperfusion by means of natriuretic peptides has been found protective in different animal models and in patients. Moreover, increasing evidence indicates that cGMP is an important step in signal transduction of endogenous cardioprotection. Thus, the cGMP pathway appears as a key element in the pathophysiology of myocardial ischaemiareperfusion and as a promising therapeutic target in patients with acute myocardial infarction.

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miR-380-5p facilitates NRF2 and attenuates cerebral ischemia/reperfusion injury-induced neuronal cell death by directly targeting BACH1

Translational Neuroscience ◽

10.1515/tnsci-2020-0172 ◽

2021 ◽

Vol 12 (1) ◽

pp. 210-217

Author(s):

Yibiao Wang ◽

Min Xu

Keyword(s):

Cell Death ◽

Cerebral Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Luciferase Assay ◽

Neuroprotective Effects ◽

Cerebral Ischemia Reperfusion

Abstract Background This study aimed to explore the role of miR-380-5p in cerebral ischemia/reperfusion (CIR) injury-induced neuronal cell death and the potential signaling pathway involved. Methodology Human neuroblastoma cell line SH-SY5Y cells were used in this study. Oxygen and glucose deprivation/reperfusion (OGD/R) model was used to mimic ischemia/reperfusion injury. CCK-8 assay and flow cytometry were used to examine cell survival. Quantitative real time PCR (RT-qPCR) assay and Western blotting were used to measure the change of RNA and protein expression, respectively. TargetScan and Luciferase assay was used to confirm the target of miR-380-5p. Malondialdehyde (MDA) superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) were measured using commercial kits. Results miR-380-5p was downregulated in SH-SY5Y cells after OGD/R. Cell viability was increased by miR-380-5p, while cell apoptosis was reduced by miR-380-5p mimics. MDA was reduced by miR-380-5p mimics, while SOD and GSHPx were increased by miR-380-5p. Results of TargetScan and luciferase assay have showed that BACH1 is the direct target of miR-380-5p. Expression of NRF2 was upregulated after OGD/R, but was not affected by miR-380-5p. mRNA expression of HO-1 and NQO1 and ARE activity were increased by miR-380-5p. Overexpression of BACH1 reversed the antioxidant and neuroprotective effects of miR-380-5p. Conclusion miR-380-5p inhibited cell death induced by CIR injury through target BACH1 which also facilitated the activation of NRF2, indicating the antioxidant and neuroprotective effects of miR-380-5p.

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