What is MPO?
Synonyms: Myeloperoxidase, Peroxidase
Overview: Sensitive and specific marker for myeloid leukemia and granulocytic sarcoma
Signal localization: cytoplasm
MPO is an important iron-containing lysosome, which exists in the aniline blue granules of myeloid cells (mainly neutrophils and monocytes) and is a specific marker of myeloid cells. With the deepening of the study of MPO, it has been found that MPO gene polymorphisms lead to differences in the susceptibility of individuals to several diseases, and are closely related to the occurrence and development of a variety of human diseases. Therefore, it has been increasingly emphasized by scholars at home and abroad.
MPO Research
MPO was cloned from human acute myeloid leukemia cells, suggesting that a single gene is responsible for its coding. MPO is located on chromosome 17. A study by Morishita et al. reported that the human MPO gene consists of 12 exons and 11 introns located in band 17q23.1. In addition, a single mRNA transcription start site was identified, homologous to the sequence of the 5-promoter region of the proto-oncogene c-myc. During the differentiation of mouse or human promyelocytic leukemia cells into granulocytes or monocytes, it has been observed that mRNAs for both MPO and c-myc decline in response to granulocyte colony-stimulating factors. It is interesting to note that other related peroxidases, including eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase, appear to be clustered in the same region, with eosinophil peroxidase located at 34 kb of the MPO and lactoperoxidase genes.
MPO proteins are tetramers with an estimated total molecular weight of 150,000 kDa. the tetramer consists of two hemiMPO consisting of two heavy (~60 kDa) and two light (~15 kDa) fractions. the tetramer is composed of two amino acids (~60 kDa) and two amino acids (~15 kDa). the tetramer is composed of two halves (hemiMPO) and two light (~15 kDa) fractions. Previously reported molecular weights have ranged from 120,000 ~ 160,000 kDa. HemiMPO has been reported to have 467 amino acids in the large chain and 105 amino acids in the short chain.
The Structure and Biological Effects of MPO
MPO is secreted by neutrophils, monocytes, and some macrophages, with polymorphonuclear leukocytes (PMNs) being its main source. Its synthesis is carried out in the bone marrow by granulocytes before they enter the circulation and is subsequently stored in azurophilic granules. MPO is a tetramer consisting of two heavy chains and two light chains and is a member of the heme peroxidase family.
MPO is a marker of neutrophil (PMN) activation, and its level and activity represent the function and state of PMN. Under physiological conditions, MPO is part of the natural immune system and fights against invasion by pathogenic bacteria and fungi. Under specific conditions, MPO can catalyze reactions to generate excess oxidants, which, when exceeding the body's antioxidant defense response, can lead to oxidative stress and oxidative tissue damage involved in a variety of diseases, such as inflammation, small vessel vasculitis, tumors, nephritis, and atherosclerosis.
The Role and Mechanism of MPO
1) Causes endothelial dysfunction
MPO catalyzes the depletion of nitric oxide (NO) and inhibits its biological activity, leading to endothelial dysfunction.
2) Oxidative modification of low density protein (LDL)
Oxidative modification of LDL is involved in the formation of atherosclerosis and is one of the important factors in atherosclerosis. Various derivatives of MPO are involved in the oxidative modification of LDL and contribute to atherosclerosis in various ways.
3) Selective modification of high-density lipoprotein (HDL)
MPO is also capable of modifying high-density lipoprotein (HDL), the only lipoprotein that provides atherosclerosis protection by transporting peripheral cholesterol back to the liver.
4) Promotion of Endothelial Cell Apoptosis and Thrombosis
Potential role of MPO and MPO-derived oxidants in promoting atherosclerotic plaque instability in the presence of plaque instability or rupture.
5) Activation of Matrix MMP
Fibrous cap thickness is a key determinant of the relative stability of atherosclerotic plaques.MPO may cause plaque instability by activating MMP and inactivating its inhibitors, leading to the degradation of the fibrous cap matrix.
6) MPO and Atherosclerotic Plaque Weakening
The vulnerability of atherosclerotic plaques depends on the integrity of the fibrous cap that covers the lipid core produced by foam cells. Derivatives of MPO can promote atherosclerotic plaque attenuation by weakening the fibrous cap.
7) MPO and coronary artery spasm
MPO directly catalyzes the consumption of NO, leading to coronary artery spasm, causing myocardial ischemia, angina pectoris, and even myocardial infarction.MPO oxidizes NO to nitrogen oxides, which accelerates oxidative damage and the rate of oxidative transformation of LDL, ultimately leading to atherosclerosis.
8) Promotion of Myocardial Dysfunction and Abnormal Ventricular Remodeling After Myocardial Infarction
Inflammation continues to play a major role in the pathology following fibrous cap rupture and luminal obstruction, with leukocytes migrating around the necrotic site, reperfusion of the occluded artery, promotion of inflammation, and increased partial pressure of oxygen, and MPO promoting reverse ventricular remodeling.
When studying MPO, scientists usually use various experimental methods to detect and measure MPO activity and expression levels. Commonly used methods include enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, and immunoblotting. These methods can help scientists to understand the changes of MPO in different diseases and physiological states, and to study its mechanism of action in depth.
At this stage, research on MPO has shown that it is of great biological significance in the pre-diagnosis and risk assessment of many diseases.MPO can cause certain diseases through various pathways, and at the same time, the distribution of gene polymorphisms can reduce the susceptibility level of the organism to certain diseases, which can protect the organism to a large extent. Therefore, the study of MPO is important for the prevention and diagnosis of many diseases.
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