P22phox

Last updated

p22phox Protein, also known as the human neutrophil cytochrome b light chain (CYBA), is an essential component of the membrane-associated enzyme phagocyte NADPH-oxidase [1] This enzyme uses NADH or NADPH as the electron donor for the one electron reduction of oxygen to produce superoxide anion, a reactive oxygen species (ROS), [2] and a functionally important step for the antimicrobial activity of phagocytic cells. [3] p22phox is also expressed in many other human cells such as endothelial and vascular smooth muscle cells, including those within the coronary arteries. [4] Specific polymorphisms of the CYBA gene have been identified that are associated with a decreased risk of coronary artery disease (CAD). [4]

Contents

Protein structure and gene function

Cytochrome b is a heterodimer of two glycoproteins, gp91phox (also known as the heavy or β chain) and p22phox (the light or α chain). The heavy and light chains are closely associated in phagocytic cells, but while the expression of gp91phox is restricted to these cells, p22phox has been detected in many other cell types [1] and is able to function as a component of NAD(P)H oxidases. [2] The alpha chain CYBA gene is located on chromosome 16q24 and consists of 6 exons and 5 introns, with a total length of 8.5kb. [1]

Oxidative stress in the vasculature induced by ROS (particularly the superoxide anion) via the NAD(P)H oxidase pathway causes vascular wall remodeling and endothelial dysfunction, consistent with the initial pathogenesis of vascular diseases such as atherosclerosis and CAD. [5] Genetic alterations in the CYBA gene have been reported that interrupt this pathway in the vasculature, including the C242T and A640G polymorphisms. [2]

The C242T polymorphism occurs in exon 4 and results in a histidine to tyrosine amino acid substitution [1] in the p22phox protein. This leads to reduced NAD(P)H oxidase activity in human blood vessels and therefore a decreased production of ROS and vascular oxidative stress. [6] A 2014 meta-analysis indicated a protective role of this polymorphism for CAD in an Asian population due to reduced NAD(P)H oxidase activity. [2]

The A640G polymorphism is located in the 3’ untranslated region (UTR) of the CYBA gene and does not cause an amino acid substitution, however it has still been shown to have an effect on ROS generation. [7] Although this variation has been less extensively studied, it has also been linked to a decreased risk of CAD, [2] possibly due to decreased translational activity of the CYBA gene. [7] Specific mechanisms of this particular polymorphism are currently under investigation. [2]

Related Research Articles

<span class="mw-page-title-main">Chronic granulomatous disease</span> Hereditary disease group

Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens. This leads to the formation of granulomas in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.

Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.

NADPH oxidase is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Human isoforms of the catalytic component of the complex include NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2.

<span class="mw-page-title-main">NOX2</span> Protein-coding gene in the species Homo sapiens

NADPH oxidase 2 (Nox2), also known as cytochrome b(558) subunit beta or Cytochrome b-245 heavy chain, is a protein that in humans is encoded by the NOX2 gene. The protein is a superoxide generating enzyme which forms reactive oxygen species (ROS).

Anthony Segal FRS FMedSci is a British physician/scientist.

<span class="mw-page-title-main">Apocynin</span> Chemical compound

Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. It has been isolated from a variety of plant sources and is being studied for its variety of pharmacological properties.

<span class="mw-page-title-main">Neutrophil cytosolic factor 2</span> Protein-coding gene in the species Homo sapiens

Neutrophil cytosol factor 2 is a protein that in humans is encoded by the NCF2 gene.

<span class="mw-page-title-main">Neutrophil cytosolic factor 1</span> Protein-coding gene in the species Homo sapiens

Neutrophil cytosol factor 1, also known as p47phox, is a protein that in humans is encoded by the NCF1 gene.

<span class="mw-page-title-main">NOX1</span> Protein-coding gene in the species Homo sapiens

NADPH oxidase 1 is an enzyme that in humans is encoded by the NOX1 gene.

<span class="mw-page-title-main">NOX4</span> Protein-coding gene in the species Homo sapiens

NADPH oxidase 4 is an enzyme that in humans is encoded by the NOX4 gene, and is a member of the NOX family of NADPH oxidases.

<span class="mw-page-title-main">Cytochrome b-245, alpha polypeptide</span> Protein-coding gene in the species Homo sapiens

Cytochrome b-245 light chain is a protein that in humans is encoded by the CYBA gene involved in superoxide production and phagocytosis.

<span class="mw-page-title-main">Neutrophil cytosolic factor 4</span> Protein-coding gene in the species Homo sapiens

Neutrophil cytosol factor 4 is a protein that in humans is encoded by the NCF4 gene.

<span class="mw-page-title-main">Dual oxidase 2</span> Protein-coding gene in the species Homo sapiens

Dual oxidase 2, also known as DUOX2 or ThOX2, is an enzyme that in humans is encoded by the DUOX2 gene. Dual oxidase is an enzyme that was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2. The protein location is not exclusive to thyroid tissue; hDUOX1 is prominent in airway epithelial cells and hDUOX2 in the salivary glands and gastrointestinal tract.

<span class="mw-page-title-main">Dual oxidase 1</span> Protein-coding gene in the species Homo sapiens

Dual oxidase 1, also known as DUOX1 or ThOX1, is an enzyme which in humans is encoded by the DUOX1 gene. DUOX1 was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2. Human DUOX protein localization is not exclusive to thyroid tissue; hDUOX1 is prominent in airway epithelial cells and hDUOX2 in the salivary glands and gastrointestinal tract.

<span class="mw-page-title-main">NOX5</span> Protein-coding gene in the species Homo sapiens

NADPH oxidase, EF-hand calcium binding domain 5, also known as NOX5, is a protein which in humans is encoded by the NOX5 gene.

<span class="mw-page-title-main">Renalase</span> Mammalian protein found in Homo sapiens

Renalase, FAD-dependent amine oxidase is an enzyme that in humans is encoded by the RNLS gene. Renalase is a flavin adenine dinucleotide-dependent amine oxidase that is secreted into the blood from the kidney.

Neutrophil oxidative burst test is a measure of neutrophil oxidation and is a useful assay in the diagnosis of chronic granulomatous disease and is also a useful means to determine the overall metabolic integrity of phagocytosing neutrophils. The NADPH oxidase enzyme is missing in CGD. From total blood, neutrophils can be purified and the NADPH oxidase activity can be measured with different methods in these cells after activation. Phagocytosis by polymorphonuclear neutrophils and monocytes constitutes an essential arm of host defense against bacterial or fungal infections. The phagocytic process can be separated into several major stages: chemotaxis, attachment of particles to the cell surface of phagocytes, ingestion (phagocytosis) and intracellular killing by oxygen-dependent and oxygen-independent mechanisms.

<span class="mw-page-title-main">20-Hydroxyeicosatetraenoic acid</span> Chemical compound

20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regulation of vascular tone, blood flow to specific organs, sodium and fluid transport in the kidney, and vascular pathway remodeling. These vascular and kidney effects of 20-HETE have been shown to be responsible for regulating blood pressure and blood flow to specific organs in rodents; genetic and preclinical studies suggest that 20-HETE may similarly regulate blood pressure and contribute to the development of stroke and heart attacks. Additionally the loss of its production appears to be one cause of the human neurological disease, hereditary spastic paraplegia. Preclinical studies also suggest that the overproduction of 20-HETE may contribute to the progression of certain human cancers, particularly those of the breast.

Edgar Pick is an Israeli immunologist who is Professor Emeritus of Immunology in the Department of Clinical Microbiology and Immunology at the Faculty of Medical and Health Sciences at Tel Aviv University, Israel.

Kidney ischemia is a disease with a high morbidity and mortality rate. Blood vessels shrink and undergo apoptosis which results in poor blood flow in the kidneys. More complications happen when failure of the kidney functions result in toxicity in various parts of the body which may cause septic shock, hypovolemia, and a need for surgery. What causes kidney ischemia is not entirely known, but several pathophysiology relating to this disease have been elucidated. Possible causes of kidney ischemia include the activation of IL-17C and hypoxia due to surgery or transplant. Several signs and symptoms include injury to the microvascular endothelium, apoptosis of kidney cells due to overstress in the endoplasmic reticulum, dysfunctions of the mitochondria, autophagy, inflammation of the kidneys, and maladaptive repair.

References

  1. 1 2 3 4 Dinauer MC, Pierce EA, Bruns GA, Curnutte JT, Orkin SH. "Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease." J Clin Invest. November 1990; 86(5): 1729-37.
  2. 1 2 3 4 5 6 Xu Q, Yuan F, Wu J. "Polymorphisms of C242T and A640G in CYBA Gene and the risk of coronary artery disease: A meta-analysis." PLoS One. 2014; 9(1): e84251
  3. ↑ Ushio-Fukai M, Zafari A, Fukui T, Ishizaka N, Griendling K. "p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II induced hypertrophy in vascular smooth muscle cells." J Bio Chem. September 20, 1996; 271: 23317-21.
  4. 1 2 Azumi H et al. "Expression of NADH/NADPH oxidase p22phox in human coronary arteries." Circulation. October 5, 1999; 100(14): 1494-8.
  5. ↑ Fortuna A, San Jose G, Moreno MU, Diez J, Zalba G. "Oxidative stress and vascular remodeling." Exp. Physiol. July 2005; 90(4): 457-62.
  6. ↑ Tomasz J, et al. "Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis." Circulation. 2000; 102: 1744 – 1747.
  7. 1 2 Bedard K, Attar H, Bonnefont J, Jaquet V, Borel C, Plastre O, Stasia MJ, Antonarakis S, Krause KH. "Three common polymorphisms in the CYBA gene form a haplotype associated with decreased ROS generation." Hum. Mutat. July 2009; 30(7): 1123-1133
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.