CYBB

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This article is about a human gene. For the airport in Canada, see Kugaaruk Airport.
Cytochrome b-245, beta polypeptide
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CYBB ; AMCBX2; CGD; GP91-1; GP91-PHOX; GP91PHOX; NOX2; p91-PHOX
External IDs OMIM300481 MGI88574 HomoloGene68054 ChEMBL: 1287627 GeneCards: CYBB Gene
RNA expression pattern
PBB GE CYBB 203923 s at tn.png
PBB GE CYBB 203922 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1536 13058
Ensembl ENSG00000165168 ENSMUSG00000015340
UniProt P04839 Q61093
RefSeq (mRNA) NM_000397 NM_007807
RefSeq (protein) NP_000388 NP_031833
Location (UCSC) Chr HG1424_PATCH:
37.64 – 37.67 Mb
Chr X:
9.44 – 9.49 Mb
PubMed search [1] [2]

Cytochrome b-245 heavy chain also known as cytochrome b(558) subunit beta or NADPH oxidase 2 or Nox2 is a protein that in humans is encoded by the CYBB gene.[1] The protein is a super-oxide generating enzyme which forms reactive oxygen species (ROS).

Function[edit]

Nox2, or Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes.[1]

Also, many of the functions for Nox2 are linked through the many functions of NADPH oxidase since Nox2 is one of the several isoforms of the gp91phox catalytic subunit of NADPH oxidase.[2]

There has been recent evidence that shows that it plays an important role in atherosclerotic lesion development in the aortic arch, thoracic, and abdominal aorta.[2]

It has also been shown to play a part in determining the size of a myocardial infarction due to its connection to ROS which play a role in myocardial reperfusion injury. This was a result of the relation between Nox2 and the signalling towards neutrophil invasion.[3] Also, it increases golbal post-reperfusion oxidative stress probably due to decreased STAT3 and Erk phosphorylation.[3]

As well, it appears that hippocampal oxidative stress is increase in septic animals due to the actions of Nox2. This connection also came about through the actions of the chemically active ROS which work as one of the main components that help in the development of neuroinflammation associated with Sepsis-associated encephalopathy (SAE).[4]

Lastly, due to recent experiments, it seems that Nox2 also plays an important role in angiotensin II-mediated inward remodelling in cerebral arterioles due to the emittance of superoxides from Nox2-containing NADPH oxidases.[5]

Clinical significance[edit]

CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this disorder, there is decreased activity of phagocyte NADPH oxidase; neutrophils are able to phagocytize bacteria but cannot kill them in the phagocytic vacuoles. The cause of the killing defect is an inability to increase the cell's respiration and consequent failure to deliver activated oxygen into the phagocytic vacuole.[1]

Since Nox2 was shown to play a huge part in determining the size of a myocardial infarction, this transforms the protein into a possible future target through drug medication due to its negative effect on myocardial reperfusion.[3]

Recent evidence highly suggests that Nox2 generates ROS which contribute to reduce flow-mediated dilation (FMD) in patients with periphery artery disease (PAD). Scientists have gone to conclude that administering an antioxidant helps with inhibiting Nox2 activity and allowing in the improvement of arterial dilation.[6]

Lastly, targeting Nox2 in the bone marrow could be a great therapeutic attempt at treating vascular injury during diabetic retinopathy (damage to the retina), because the Nox2-generated ROS which are produced by the bone-marrow derived cells & local retinal cells are accumulating the vascular injury in the diabetic retina area.[6]

Interactions[edit]

Nox2 has been shown to interact directly with podocyte TRPC6 channels.[7]

References[edit]

  1. ^ a b c "Entrez Gene: CYBB cytochrome b-245, beta polypeptide (chronic granulomatous disease)". 
  2. ^ a b "Nox2 is required for macrophage chemotaxis towards CSF-1". 
  3. ^ a b c Braunersreuther V, Montecucco F, Asrih M, Pelli G, Galan K, Frias M, Burger F, Quinderé AL, Montessuit C, Krause KH, Mach F, Jaquet V. (Nov 2013). "Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury". J Mol Cell Cardiol. 64: 99–107. doi:10.1016/j.yjmcc.2013.09.007. PMID 24051369. 
  4. ^ Hernandes MS, D'Avila JC, Trevelin SC, Reis PA, Kinjo ER, Lopes LR, Castro-Faria-Neto HC, Cunha FQ, Britto LR, Bozza FA. (27 Feb 2014). "The role of Nox2-derived ROS in the development of cognitive impairment after sepsis". J Neuroinflammation. 11 (1): 36. doi:10.1186/1742-2094-11-36. PMID 24571599. 
  5. ^ Chan SL, Baumbach GL. (26 June 2013). "Deficiency of Nox2 prevents angiotensin II-induced inward remodeling in cerebral arterioles". Front Physiol. 4: 133. doi:10.3389/fphys.2013.00133. PMC 3693079. PMID 23805104. 
  6. ^ a b Loffredo L, Carnevale R, Cangemi R, Angelico F, Augelletti T, Di Santo S, Calabrese CM, Della Volpe L, Pignatelli P, Perri L, Basili S, Violi F. (30 April 2013). "NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease". Int J Cardiol. 165 (1): 184–92. doi:10.1016/j.ijcard.2012.01.069. PMID 22336250. 
  7. ^ Kim EY, Anderson M, Wilson C, Hagmann H, Benzing T, Dryer SE. (1 Nov 2013). "NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.". Am J Physiol Cell Physiol. 305 (9): C960–71. doi:10.1152/ajpcell.00191.2013. PMID 23948707. 

Further reading[edit]

External links[edit]