Na+ overload-induced mitochondrial damage in the ischemic heart

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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Selective β 2 -Adrenoreceptor Stimulation Attenuates Myocardial Cell Death and Preserves Cardiac Function After Ischemia–Reperfusion Injury

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.112.251769 ◽

2012 ◽

Vol 32 (8) ◽

pp. 1865-1874 ◽

Cited By ~ 20

Author(s):

Shashi Bhushan ◽

Kazuhisa Kondo ◽

Benjamin L. Predmore ◽

Maxim Zlatopolsky ◽

Adrienne L. King ◽

...

Keyword(s):

Cell Death ◽

Cardiac Function ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Cell

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Phospholipid oxidation products in ferroptotic myocardial cell death

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00076.2019 ◽

2019 ◽

Vol 317 (1) ◽

pp. H156-H163 ◽

Cited By ~ 5

Author(s):

Aleksandra Stamenkovic ◽

Grant N. Pierce ◽

Amir Ravandi

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Myocardial Cell ◽

Oxidation Products ◽

Oxygen Species ◽

New Therapeutic Approaches

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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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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