Myeloperoxidase: Bridging the gap in neurodegeneration

Ray, Rashmi; Katyal, Anju

doi:10.1016/j.neubiorev.2016.06.031

Cited by 79 publications

(61 citation statements)

References 155 publications

(208 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Myeloperoxidase is a highly abundant iron containing heme protein that is encoded by 14Kb gene located on the chromosome 17q23.1 [18]. The proteolytic form of the enzyme is 146 kDa and is most abundant in phagocytic cells [19,20].…”

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease

et al. 2017

View full text Add to dashboard Cite

Background: The role of myeloperoxidase in chronic kidney disease (CKD) and its association with coronary artery disease (CAD) is controversial. In this study, we compared myeloperoxidase and protein-bound 3-chlorotyrosine (ClY) levels in subjects with varying degrees of CKD and tested their associations with CAD. Methods: From Clinical Phenotyping Resource and Biobank Core, 111 patients were selected from CKD stages 1 to 5. Plasma myeloperoxidase level was measured using enzyme-linked-immunosorbent assay. Plasma protein-bound 3-ClY, a specific product of hypochlorous acid generated by myeloperoxidase was measured by liquid chromatography mass spectrometry. Results: We selected 29, 20, 24, 22, and 16 patients from stages 1 to 5 CKD, respectively. In a sex-adjusted general linear model, mean ± SD of myeloperoxidase levels decreased from 18.1 ± 12.3 pmol in stage 1 to 10.9 ± 4.7 pmol in stage 5 (p = 0.011). In patients with and without CAD, the levels were 19.1 ± 10.1 and 14.8 ± 8.7 pmol (p = 0.036). There was an increase in 3-ClY mean from 0.81 ± 0.36 mmol/mol-tyrosine in stage 1 to 1.42 ± 0.41 mmol/mol-tyrosine in stage 5 (p < 0.001). The mean 3-ClY levels in patients with and without CAD were 1.25 ± 0.44 and 1.04 ± 0.42 mmol/mol-tyrosine (p = 0.023), respectively. C-statistic of ClY when added to myeloperoxidase level to predict CKD stage 5 was 0.86, compared to 0.79 for the myeloperoxidase level alone (p = 0.0097). Conclusion: The myeloperoxidase levels decrease from stages 1 to 5, whereas activity increases. In contrast, both myeloperoxidase and ClY levels rise in the presence of CAD at various stages of CKD. Measuring both plasma myeloperoxidase and 3-CLY levels provide added value to determine the burden of myeloperoxidase-mediated oxidative stress.

show abstract

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Due to its high toxicity, HOCl released by neutrophils into the phagosome seems to have a high impact in fighting against microbial pathogens and controlling the bacterial population in the host [42]. However, the impaired homeostasis between oxidants and antioxidants, in favor of ROS production, leads to an uncontrolled generation of HOCl, which is associated with chronic inflammatory diseases (Figure 2), may have carcinogenic and mutagenic potential [43], and is even known as a stable but highly reactive neurotoxic oxidant in the brain, where HOCl reacts rapidly with H 2 O 2 , O 2 ∙− or nitrite generating 1 O 2 , HO ∙ , or nitryl chloride (NO 2 Cl) that may contribute to extensive tissue damage [44]. Due to its fast homeostatic consumption, in vivo generated HOCl cannot be measured directly, but either as stable scavenger products or via the determination of the MPO activity in the corresponding body fluid, for instance, by using the well-known conversion of guaiacol into tetrahydroguaiacol [45].…”

Section: In Vivo Generation Of Hocl By the Mpo-h2o2 Systemmentioning

confidence: 99%

“…These cytotoxic effects (i.e., frameshift mutations or base pair substitutions) can be caused by both lipid peroxidation products and HOCl-mediated protein-DNA crosslinks. Under neuropathological conditions, HOCl is continuously released from PMNs or microglia to diffuse into the brain parenchyma and maintains chlorinative stress resulting in neurodegeneration [44]. Even if noncovalent ionic interactions of DNA and proteins are physiologically very important for normal cellular functions [85], the oxidation of covalently bound protein-DNA cross linkages leads to inadequate DNA repair [86] and to mutagenic and cytotoxic effects of phagocytes on microbial pathogens and host tissue [87].…”

Section: Reactivity Of In Vivo Generated Hoclmentioning

confidence: 99%

Chlorinated Phospholipids and Fatty Acids: (Patho)physiological Relevance, Potential Toxicity, and Analysis of Lipid Chlorohydrins

Schröter

Schiller

2016

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Chlorinated phospholipids are formed by the reaction of hypochlorous acid (HOCl), generated by the enzyme myeloperoxidase under inflammatory conditions, and the unsaturated fatty acyl residues or the head group. In the first case the generated chlorohydrins are both proinflammatory and cytotoxic, thus having a significant impact on the structures of biomembranes. The latter case leads to chloramines, the properties of which are by far less well understood. Since HOCl is also widely used as a disinfecting and antibacterial agent in medicinal, industrial, and domestic applications, it may represent an additional source of danger in the case of abuse or mishandling. This review discusses the reaction behavior of in vivo generated HOCl and biomolecules like DNA, proteins, and carbohydrates but will focus on phospholipids. Not only the beneficial and pathological (toxic) effects of chlorinated lipids but also the importance of these chlorinated species is discussed. Some selected cleavage products of (chlorinated) phospholipids and plasmalogens such as lysophospholipids, (chlorinated) free fatty acids and α-chloro fatty aldehydes, which are all well known to massively contribute to inflammatory diseases associated with oxidative stress, will be also discussed. Finally, common analytical methods to study these compounds will be reviewed with focus on mass spectrometric techniques.

show abstract

“…14,15 The number of cells that produce MPO in the brain increases in the areas of nervous tissue destruction during the growth of malignant tumours, in Alzheimer and Parkinson diseases. 17,18 Thus, HOCl can be generated in the brain at various pathologies, thereby increasing the probability of sphingolipids' destruction with the formation of 2HD. 17,18 Thus, HOCl can be generated in the brain at various pathologies, thereby increasing the probability of sphingolipids' destruction with the formation of 2HD.…”

mentioning

confidence: 99%

“…16 The source of HOCl in the brain is neuronal MPO, localized in neurons and microglial cells. 17,18 Thus, HOCl can be generated in the brain at various pathologies, thereby increasing the probability of sphingolipids' destruction with the formation of 2HD. The effect of 2HD on central nervous system (CNS) cells functions under normal and pathological conditions has not yet been studied.…”

mentioning

confidence: 99%

2‐Hexadecenal inhibits growth of C6 glioma cells

Семенкова

Kvacheva

Lisovskaya

et al. 2019

Cell Biochemistry & Function

View full text Add to dashboard Cite

2-Hexadecenal (2HD) formation in the organism occurs via irreversible enzymatic degradation of sphingosine-1-phosphate or nonenzymatic γ-, UV-, or HOCl-induced destruction of a number of sphingolipids including S1P. The current research focuses on the study of 2HD effects on C6 glioma cells growth. The results obtained show that 2HD causes a dose-dependent decrease in proliferative and mitotic indices.The change in the mitotic index is due to the redistribution of cells in the different phases of mitosis. These processes are accompanied by cytoskeleton rearrangement and changes in cell morphology, which are expressed in F-actin redistribution, change in the number and type of filopodia and fibrils, leading to cell shape changes, decrease in intercellular contacts and monolayer rarefaction. Cells treatment with 2HD leads to apoptosis induction and signalling pathways modification, including activation of JNK, p38, and ERK1/2 MAPK but not PI3K. The effects observed are not related to the cytotoxicity of 2HD. Significance of the study: 2HD-an unsaturated aldehyde, which level can rise under conditions of oxidative stress as a result of nonenzymatic sphingolipids' destruction. The mechanisms of 2HD action on various cell types have not been sufficiently studied. Therefore, the study on functional role of this aldehyde in different cell types that may be its target is relevant. This study demonstrated that 2HD inhibits growth of C6 glioma cells due to modification of intracellular processes of signal transduction, cytoskeleton rearrangement, change in the mitotic regimen and apoptosis induction.

show abstract

Myeloperoxidase: Bridging the gap in neurodegeneration

Cited by 79 publications

References 155 publications

Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease

Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease

Chlorinated Phospholipids and Fatty Acids: (Patho)physiological Relevance, Potential Toxicity, and Analysis of Lipid Chlorohydrins

2‐Hexadecenal inhibits growth of C6 glioma cells

Contact Info

Product

Resources

About