Myeloperoxidase promotes tube formation, triggers ERK1/2 and Akt pathways and is expressed endogenously in endothelial cells

Khalil, Alia; Medfai, Hayfa; Poelvoorde, Philippe; Kazan, Mohammad Fayyad; Delporte, Cédric; Antwerpen, Pierre Van; El-Makhour, Yolla; Biston, Patrick; Delrée, P.; Badran, Bassam; Vanhamme, Luc; Boudjeltia, Karim Zouaoui

doi:10.1016/j.abb.2018.07.011

Cited by 23 publications

(24 citation statements)

References 38 publications

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“…Notably, MPO is involved in multiple pathways in different cell types and its role is not limited only to regulation of ROS production. For example, MPO treatment is shown to activate ERK/ Akt pathway, p38 MAPK activation and enhanced nuclear translocation of NF-κB [52,53]. In our studies, although treatment with TG6-44 was effective in suppressing virus infectivity and virus-induced inflammation in our in vitro cell culture model, the specific signaling pathways leading to ROS inhibition and other observed effects are not clear.…”

Section: Plos Onementioning

confidence: 58%

Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival

et al. 2021

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Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.

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Section: Plos Onementioning

confidence: 58%

Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival

et al. 2021

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“…While it is clear that inflammation has many consequences, as far as EC are concerned, there is a well-documented interplay between inflammation and angiogenesis [27]. Inflammation driven angiogenesis has been reported and for example MPO, secreted by neutrophils at inflamed sites, stimulated the angiogenic process in endothelial cells [35,36]. Thrombin also induced angiogenesis in endothelial cells [37].…”

Section: Discussionmentioning

confidence: 99%

Apoliporotein L3 interferes with endothelial tube formation via regulation of ERK1/2, FAK and Akt signaling pathway

et al. 2018

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Members of the Apolipoprotein L family (APOL) are induced in endothelial cells by a variety of inflammatory stimuli. • APOL3 is the only APOL commonly induced by atherogenic stimuli such as thrombin, MPO or oxidized LDL. • APOL3 is also induced by angiogenic stimuli such as VEGF and FGF. • APOL3 invalidation decreases tubulogenesis and endothelial wound repair. It increases endothelial permeability. • APOL3 invalidation correlates with inhibition of pro-angiogenic pathways and reduces expression of pro-angiogenic genes.

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“…In pathological conditions, MPO has also been detected in cells outside the myeloid lineage, including endothelial cells [ 103 , 107 ], neurons [ 108 , 109 ], prostate tissue [ 110 ], and astrocytes [ 111 ]. Additionally, endocardial endothelial expression of MPO has also been observed following oxidative stress, both in tissue culture and in post-infarcted human heart tissue [ 103 ].…”

Section: Inflammation and Oxidative Stress: Myeloperoxidase And Rementioning

confidence: 99%

“…These signaling pathways are known to be redox sensitive, with increased oxidative stress due to inflammation, including the production of MPO-derived oxidants, leading to increased activation [ 136 ]. Both treatment of endothelial cells with MPO [ 107 ] and VSMC with HOCl has been shown to result in increased phosphorylation of ERK1/2 [ 137 ]. Thus, increased MPO can also indirectly increase MMP expression through ERK1/2 signaling.…”

Section: Mpo-associated Oxidative Stress and Links To Taa Pathogenmentioning

confidence: 99%

The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms

Malecki

Hambly

Jeremy

et al. 2020

IJMS

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Genetically triggered thoracic aortic aneurysms (TAAs) are usually considered to exhibit minimal levels of inflammation. However, emerging data demonstrate that specific features of an inflammatory response can be observed in TAA, and that the extent of the inflammatory response can be correlated with the severity, in both mouse models and in human studies. Myeloperoxidase (MPO) is a key mediator of the inflammatory response, via production of specific oxidative species, e.g., the hypohalous acids. Specific tissue modifications, mediated by hypohalous acids, have been documented in multiple cardiovascular pathologies, including atherosclerosis associated with coronary artery disease, abdominal aortic, and cerebral aneurysms. Similarly, data are now emerging that show the capacity of MPO-derived oxidative species to regulate mechanisms important in TAA pathogenesis, including alterations in extracellular matrix homeostasis, activation of matrix metalloproteinases, induction of endothelial dysfunction and vascular smooth muscle cell phenotypic switching, and activation of ERK1/2 signaling. The weight of evidence supports a role for inflammation in exacerbating the severity of TAA progression, expanding our understanding of the pathogenesis of TAA, identifying potential biomarkers for early detection of TAA, monitoring severity and progression, and for defining potential novel therapeutic targets.

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Myeloperoxidase promotes tube formation, triggers ERK1/2 and Akt pathways and is expressed endogenously in endothelial cells

Cited by 23 publications

References 38 publications

Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival

Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival

Apoliporotein L3 interferes with endothelial tube formation via regulation of ERK1/2, FAK and Akt signaling pathway

The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms

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