Characterization of the cellular effects of myeloperoxidase-derived oxidants on H9c2 cardiac myoblasts

Reyes, Leila; Hawkins, Clare L.; Rayner, Benjamin S.

doi:10.1016/j.abb.2019.03.004

Cited by 12 publications

(10 citation statements)

References 71 publications

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“…We have previously demonstrated that the concentration of HOCl required to elicit detrimental changes to H9c2 cells was between 40 µM and 50 µM [58]. The ability of SeMet to protect against cellular damage induced by these concentrations of HOCl in H9c2 cells was first assessed by examining mitochondrial function with flow cytometry and JC-1 staining.…”

Section: Resultsmentioning

confidence: 99%

Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

et al. 2019

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Oxidative stress is a major hallmark of cardiac ischemia/reperfusion (I/R) injury. This partly arises from the presence of activated phagocytes releasing myeloperoxidase (MPO) and its production of hypochlorous acid (HOCl). The dietary supplement selenomethionine (SeMet) has been shown to bolster endogenous antioxidant processes as well as readily react with MPO-derived oxidants. The aim of this study was to assess whether supplementation with SeMet could modulate the extent of cellular damage observed in an in vitro cardiac myocyte model exposed to (patho)-physiological levels of HOCl and an in vivo rat model of cardiac I/R injury. Exposure of the H9c2 cardiac myoblast cell line to HOCl resulted in a dose-dependent increase in necrotic cell death, which could be prevented by SeMet supplementation and was attributed to SeMet preventing the HOCl-induced loss of mitochondrial inner trans-membrane potential, and the associated cytosolic calcium accumulation. This protection was credited primarily to the direct oxidant scavenging ability of SeMet, with a minor contribution arising from the ability of SeMet to bolster cardiac myoblast glutathione peroxidase (GPx) activity. In vivo, a significant increase in selenium levels in the plasma and heart tissue were seen in male Wistar rats fed a diet supplemented with 2 mg kg−1 SeMet compared to controls. However, SeMet-supplementation demonstrated only limited improvement in heart function and did not result in better heart remodelling following I/R injury. These data indicate that SeMet supplementation is of potential benefit within pathological settings where excessive HOCl is known to be generated but has limited efficacy as a therapeutic agent for the treatment of heart attack.

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Section: Resultsmentioning

confidence: 99%

Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

et al. 2019

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“…Furthermore, HOCl and other hypohalous acids can dysregulate multiple intercellular signalling pathways, including kinase signalling (p38 and Erk2) [ 13 ] and inactivation of protein tyrosine phosphatase (PTP) [ 14 ]. HOCl can also influence cell viability, as cultured cardiomyocytes or endothelial cells demonstrate increased cell apoptosis and necrosis in the presence of HOCl [ 15 , 16 ]. Therefore, the modification of amino acid residues, disruption of the phosphoproteome balance, depletion of the antioxidant pool, increase in inflammation and fibrosis, and dysregulation of endothelial function all impair cellular and mitochondrial function and result in cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats

Kazzi

Shi

Vuong

et al. 2020

IJMS

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Reperfusion therapy increases survival post-acute myocardial infarction (AMI) while also stimulating secondary oxidant production and immune cell infiltration. Neutrophils accumulate within infarcted myocardium within 24 h post-AMI and release myeloperoxidase (MPO) that catalyses hypochlorous acid (HOCl) production while increasing oxidative stress and inflammation, thereby enhancing ventricular remodelling. Nitroxides inhibit MPO-mediated HOCl production, potentially ameliorating neutrophil-mediated damage. Aim: Assess the cardioprotective ability of nitroxide 4-methoxyTEMPO (4MetT) within the setting of AMI. Methods: Male Wistar rats were separated into 3 groups: SHAM, AMI/R, and AMI/R + 4MetT (15 mg/kg at surgery via oral gavage) and subjected to left descending coronary artery ligation for 30 min to generate an AMI, followed by reperfusion. One cohort of rats were sacrificed at 24 h post-reperfusion and another 28 days post-surgery (with 4MetT (15 mg/kg) administration twice daily). Results: 3-chlorotyrosine, a HOCl-specific damage marker, decreased within the heart of animals in the AMI/R + 4-MetT group 24 h post-AMI, indicating the drug inhibited MPO activity; however, there was no evident difference in either infarct size or myocardial scar size between the groups. Concurrently, MPO, NfκB, TNFα, and the oxidation marker malondialdehyde increased within the hearts, with 4-MetT only demonstrating a trend in decreasing MPO and TNF levels. Notably, 4MetT provided a significant improvement in cardiac function 28 days post-AMI, as assessed by echocardiography, indicating potential for 4-MetT as a treatment option, although the precise mechanism of action of the compound remains unclear.

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“…However, the classical RAS together with aldosterone are chiefly responsible for maintenance of systemic arterial blood pressure and body fluid homeostasis, while the tissue RAS governs the entire activities of the body tissue concerned [14••, 20••]. A drop in arterial pressure activates the release of renin into the circulatory system where it acts on angiotensinogen (formed in the liver) to convert it to angiotensin I (Ang I) [17,21,22]. The angiotensin-converting enzyme (ACE) receptors occur in the endothelial cells of the circulatory system [20••, 23••], and the secretion of ACE occurs in the lungs' endothelial cells where it converts Ang I to Ang II [24].…”

Section: Angiotensin-converting Enzymementioning

confidence: 99%

The Renin-Angiotensin System, Hypertension, and SARS-CoV-2 Infection: a Review

2021

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Purpose of Review This review focuses on the associations between the renin-angiotensin system, hypertension, and severe acute respiratory syndrome (SARS-COV-2) infection. A brief prelude on the current state of affairs with COVID-19 is given. In addition to an overview of ACE2, Ang II, and Ang (1-7), this review presents a brief statement on hypertension, including the function of enzymes involved in the control of hypertension, cardiovascular disease, diabetes mellitus, and other malignancies. Recent Findings There is currently no data in support of the concerns raised with the use of ACEIs/ARBs. Many researchers have voiced concerns that the use of ACEIs and ARBs may increase tissue ACE2 levels. These researchers therefore recommend that individuals on ACEIs/ARB's medications withhold such antihypertensive drugs, unless advised by their physicians to do so. Summary SARS-CoV-2 uses ACE2 receptors as the port of entry to human hosts. ACE2 and ACE are different enzymes and ACE inhibitors do not inhibit ACE2. Therefore, the use of ARB's or ACEIs should not be discontinued if an individual is infected by SARS-CoV-2. Further studies are required to investigate the effect of ACEIs and ARBs on ACE2 expression and COVID-19. Keywords Renin-angiotensin system . Hypertension . SARS-COV-2 . Angiotensin-converting enzyme inhibitors . Angiotensin II This article is part of the Topical Collection on Blood Pressure Monitoring and Management * Jagidesa Moodley

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Characterization of the cellular effects of myeloperoxidase-derived oxidants on H9c2 cardiac myoblasts

Cited by 12 publications

References 71 publications

Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats

The Renin-Angiotensin System, Hypertension, and SARS-CoV-2 Infection: a Review

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