MPO

Official Full Name

myeloperoxidase

Organism

Homo sapiens

Gene ID

4353

Background

Myeloperoxidase (MPO) is a heme protein synthesized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Produced as a single chain precursor, myeloperoxidase is subsequently cleaved into a light and heavy chain. The mature myeloperoxidase is a tetramer composed of 2 light chains and 2 heavy chains. This enzyme produces hypohalous acids central to the microbicidal activity of neutrophils. [provided by RefSeq, Nov 2014]

Synonyms

MPO; myeloperoxidase

Bio Chemical Class

Peroxidases

Protein Sequence

MGVPFFSSLRCMVDLGPCWAGGLTAEMKLLLALAGLLAILATPQPSEGAAPAVLGEVDTSLVLSSMEEAKQLVDKAYKERRESIKQRLRSGSASPMELLSYFKQPVAATRTAVRAADYLHVALDLLERKLRSLWRRPFNVTDVLTPAQLNVLSKSSGCAYQDVGVTCPEQDKYRTITGMCNNRRSPTLGASNRAFVRWLPAEYEDGFSLPYGWTPGVKRNGFPVALARAVSNEIVRFPTDQLTPDQERSLMFMQWGQLLDHDLDFTPEPAARASFVTGVNCETSCVQQPPCFPLKIPPNDPRIKNQADCIPFFRSCPACPGSNITIRNQINALTSFVDASMVYGSEEPLARNLRNMSNQLGLLAVNQRFQDNGRALLPFDNLHDDPCLLTNRSARIPCFLAGDTRSSEMPELTSMHTLLLREHNRLATELKSLNPRWDGERLYQEARKIVGAMVQIITYRDYLPLVLGPTAMRKYLPTYRSYNDSVDPRIANVFTNAFRYGHTLIQPFMFRLDNRYQPMEPNPRVPLSRVFFASWRVVLEGGIDPILRGLMATPAKLNRQNQIAVDEIRERLFEQVMRIGLDLPALNMQRSRDHGLPGYNAWRRFCGLPQPETVGQLGTVLRNLKLARKLMEQYGTPNNIDIWMGGVSEPLKRKGRVGPLLACIIGTQFRKLRDGDRFWWENEGVFSMQQRQALAQISLPRIICDNTGITTVSKNNIFMSNSYPRDFVNCSTLPALNLASWREAS

Open

Disease

Chronic obstructive pulmonary disease, Heart failure, Left ventricular failure, Multiple sclerosis, Parkinsonism, Postoperative inflammation

Approved Drug

Clinical Trial Drug

4 +

Discontinued Drug

1 +

Cat.No.	Product Name	Price
CSC-DC009678	Panoply™ Human MPO Knockdown Stable Cell Line	Inquiry
CSC-SC009678	Panoply™ Human MPO Over-expressing Stable Cell Line	Inquiry
CSC-RT2791	Human MPO Knockout Cell Line - MOLM-13	Inquiry

Cat.No.	Product Name	Price
AD10106Z	Human Mpo adenoviral particles	Inquiry
LV18474L	human MPO (NM_000250) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH343920	shRNA set against Rat Mpo (NM_001107036.1)	Inquiry
SHH343916	shRNA set against Mouse Mpo (NM_010824.2)	Inquiry
SHH343912	shRNA set against Human Mpo (NM_000250.1)	Inquiry

Cat.No.	Product Name	Price
RP00014	Recombinant Mouse MPO (C-10His)	Inquiry
RP00184	Recombinant Human MPO (C-10His)	Inquiry

Cat.No.	Product Name	Price
CDFH011698	Human MPO cDNA Clone(NM_000250.1)	Inquiry
CDFR006747	Rat Mpo cDNA Clone(NM_001107036.1)	Inquiry
MiUTR1H-06398	MPO miRNA 3'UTR clone	Inquiry
CDCB193210	Rabbit MPO ORF clone (XM_002719094.2)	Inquiry
CDCH390311	Mouse MPO ORF clone(NM_010824.2)	Inquiry
CDCL133643	Human MPO ORF clone (NM_000250.1)	Inquiry
CDCR373769	Rat Mpo ORF Clone(NM_001107036.1)	Inquiry
CDCS405525	Human MPO ORF Clone (BC130476)	Inquiry

Cat.No.	Product Name	Price
CC-891	MPO Easy KO Kit	Inquiry

Detailed Information

Myeloperoxidase (MPO) is an inflammatory responsive substance secreted by promyel granules (also known as primary particles) in promyelocytes, juvenile monocytes, young lymphocytes, and young macrophages. The highest levels of promyelocytic cells, followed by primitive granulocytes, naive and primordial monocytes, are related to the neutrophil differentiation cycle.

Biological Function of MPO

Inflammation and stress, under the action of chemokines and activators, neutrophils deform and penetrate the capillaries, accumulate in the inflammation site, release the MPO to the extracellular cells or phagocytose the senescent cells and pathogenic microorganisms to form phagosomes. At the site of inflammation, MPO catalyzes the production of HOCI by H2O2 using hydrogen peroxide (H2O2)-MPO-hypochlorous acid (HOCI) pathway. HOCI reacts with the amino group of peptide and amino acid to form chloramine (NH2CI). NH2CI not only enhances immunity, but also has a strong anti-microbial effect. Therefore, under physiological conditions, MPO and H2O2, HOCI play an important role in the body's defense. However, at the same time, the generated active oxygen causes damage to normal tissues such as endothelial cells, lipids, and DNA when it is removed from the body, resulting in various diseases such as atherosclerosis, leukemia, nephritis, polyinflammatory disease, and tumors.

Figure 1. Atherosclerotic contributions of myeloperoxidase.（Taylor., et al. 2016）

MORC3 and Disease

In the presence of inflammation, neutrophils activate, MPO is released, and MPO reacts with H2O2 of neutrophil respiratory burst oxidase to produce HOCl and other oxidizing substances. Under physiological conditions, HOCI is the main oxidant of the body, which strongly reacts with tissues during inflammatory diseases to cause tissue damage. The role of MPO in atherosclerosis includes: (1) leading to endothelial dysfunction; release of inflammatory factors, causing inflammatory cells such as neutrophils to aggregate to the endothelium; neutrophils release MPO-derived HOCI to induce endothelial cell withering Endothelial dysfunction is caused by death, endothelial cell oxidative enzyme uncoupling, and reduction of NO bioavailability; (2) modifying high-density lipoprotein (HDL) to dysfunctional oxHDL; (3) converting oxidized low-density lipoprotein (LDL) into oxLDL that is more apt to cause atherosclerosis; (4) consuming nitric oxide (NO) In the inflammation, MPO-derived HOCI not only reacts with L-arginine, but also competes with NOS for the chlorinated arginine produced by the substrate, and also inhibits NOS activity, further reduces NO synthesis, and relies on vasodilation. (5) Inducing endothelial cell death and tissue factor expression involved in plaque vulnerability.

MPO and Coronary Heart Disease

Mass spectrometry analysis demonstrated that HDL isolated from patients with established cardiovascular disease contained high levels of 3-chlorinated tyrosine and 3-nitrotyrosine, two of the characteristic products of MPO. When HDL's major carrier apoA-I is oxidized by MPO, the ability to push cellular cholesterol out of ABCA1 is impaired.

Studies have shown that 885 patients who underwent selective coronary angiography were followed for at least 13 years, and cardiovascular mortality was observed by monitoring MPO levels. The results showed that patients with high levels of MPO had a cardiovascular mortality rate 2.4 times that of patients with low levels of MPO. The combination of MPO and C-reactive protein (CRP) is a better predictor of long-term cardiovascular events, and the increase in both is 4.3 times higher than the accuracy of predicting cardiovascular risk at a single level. Patients with AMI (acute myocardial infarction) have increased neutrophil activity, increased MPO secretion and cause myocardial damage. For patients with low levels of troponin T (TnT) but myocardial damage, serum free MPO levels predict adverse cardiovascular events.

References:

Taylor, & Angela, M.. (2016). The resurrection of myeloperoxidase as a therapeutic target. JACC: Basic to Translational Science, 1(7), 644-646.
Amjad, K. , Mohammed, A. , & Arshad, R. . (2018). Myeloperoxidase as an active disease biomarker: recent biochemical and pathological perspectives. Medical Sciences, 6(2), 33-.
Long, L. , & Song, Y. . (2017). Myeloperoxidase: a promising therapeutic target in prevention of atherosclerosis. International Journal of Cardiology, 256, 15.

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