Elastase
In molecular biology, elastase is an enzyme from the class of proteases (peptidases) that break down proteins. In particular, it is a serine protease.
- Bieth JG (2001). “[The elastases]”. J. Soc. Biol. (in French). 195 (2): 173–9. doi:10.1051/jbio/2001195020173. PMID 11723830.
- Bruce, Alberts (2014-11-18). Molecular biology of the cell (Sixth ed.). New York, NY. ISBN 9780815344322. OCLC 887605755.
Forms and classification
Eight human genes exist for elastase:
| Family | Gene symbol | Protein name | EC number | ||
|---|---|---|---|---|---|
| Approved | Previous | Approved | Previous | ||
| chymotrypsin- like | CELA1 | ELA1 | chymotrypsin-like elastase family, member 1 | elastase 1, pancreatic | EC 3.4.21.36 |
| CELA2A | ELA2A | chymotrypsin-like elastase family, member 2A | elastase 2A, pancreatic | EC 3.4.21.71 | |
| CELA2B | ELA2B | chymotrypsin-like elastase family, member 2B | elastase 2B, pancreatic | EC 3.4.21.71 | |
| CELA3A | ELA3A | chymotrypsin-like elastase family, member 3A | elastase 3A, pancreatic | EC 3.4.21.70 | |
| CELA3B | ELA3B | chymotrypsin-like elastase family, member 3B | elastase 3B, pancreatic | EC 3.4.21.70 | |
| chymotrypsin | CTRC | ELA4 | chymotrypsin C (caldecrin) | elastase 4 | EC 3.4.21.2 |
| neutrophil | ELANE | ELA2 | neutrophil elastase | elastase 2 | EC 3.4.21.37 |
| macrophage | MMP12 | HME | macrophage metalloelastase | macrophage elastase | EC 3.4.24.65 |
Some bacteria (including Pseudomonas aeruginosa) also produce elastase. In bacteria, elastase is considered a virulence factor.
Function
Elastase breaks down elastin, an elastic fibre that, together with collagen, determines the mechanical properties of connective tissue. The neutrophil form breaks down the Outer membrane protein A (OmpA) of E. coli and other Gram-negative bacteria. Elastase also has the important immunological role of breaking down Shigella virulence factors. This is accomplished through the cleavage of peptide bonds in the target proteins. The specific peptide bonds cleaved are those on the carboxyl side of small, hydrophobic amino acids such as glycine, alanine, and valine. For more on how this is accomplished, see serine protease.
The role of human elastase in disease
A1AT
Elastase is inhibited by the acute-phase protein α1-antitrypsin (A1AT), which binds almost irreversibly to the active site of elastase and trypsin. A1AT is normally secreted by the liver cells into the serum. Alpha-1 antitrypsin deficiency (A1AD) leads to uninhibited destruction of elastic fibre by elastase; the main result is emphysema.
Cyclic neutropenia
The rare disease cyclic neutropenia (also called “cyclic hematopoeiesis”) is an autosomal dominant genetic disorder characterised by fluctuating neutrophil granulocyte counts over 21-day periods. During neutropenia, patients are at risk for infections. In 1999, this disease was linked to disorders in the ELA-2 / ELANE gene. Other forms of congenital neutropenia also appear to be linked to ELA-2 mutations.[citation needed]
- Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC (1999). “Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis”. Nat. Genet. 23 (4): 433–6. doi:10.1038/70544. PMID 10581030. S2CID 6951666.
Other diseases
Neutrophil elastase is responsible for the blistering in bullous pemphigoid, a skin condition, in the presence of antibodies. It may also play a role in the formation of abdominal aortic aneurysms (AAAs) and chronic obstructive pulmonary disease (COPD).
The role of bacterial elastase in disease
Elastase has been shown to disrupt tight junctions, cause proteolytic damage to tissue, break down cytokines and alpha proteinase inhibitor, cleave immunoglobulin A and G (IgA, IgG), and cleave both C3bi, a component of the complement system, and CR1, a receptor on neutrophils for another complement molecule involved in phagocytosis. The cleavage of IgA, IgG, C3bi, and CR1 contributes to a decrease of the ability of neutrophils to kill bacteria by phagocytosis. Together, all these factors contribute to human pathology.
Gold sodium thiomalate
Sodium aurothiomalate (INN, known in the United States as gold sodium thiomalate) is a gold compound that is used for its immunosuppressive anti-rheumatic effects. Along with an orally-administered gold salt, auranofin, it is one of only two gold compounds currently employed in modern medicine. Its precise mechanism of action is unknown but is known that it inhibits the synthesis of prostaglandins. It also modulates phagocytic cells and inhibits class II major histocompatibility complex-peptide interactions. It is also known that it inhibits the following enzymes:
- Acid phosphatase
- Beta-glucuronidase
- Elastase
- Cathepsin G
- Thrombin
- Microsomal prostaglandin E synthase-1
- Jessop JD, O’Sullivan MM, Lewis PA, Williams LA, Camilleri JP, Plant MJ, Coles EC (September 1998). “A long-term five-year randomized controlled trial of hydroxychloroquine, sodium aurothiomalate, auranofin and penicillamine in the treatment of patients with rheumatoid arthritis”. British Journal of Rheumatology. 37 (9): 992–1002. doi:10.1093/rheumatology/37.9.992. PMID 9783766.
- Iqbal MS, Saeed M, Taqi SG (2008). “Erythrocyte membrane gold levels after treatment with auranofin and sodium aurothiomalate”. Biological Trace Element Research. 126 (1–3): 56–64. doi:10.1007/s12011-008-8184-x. PMID 18649049. S2CID 20169992.
- Kean WF, Kean IR (June 2008). “Clinical pharmacology of gold”. Inflammopharmacology. 16 (3): 112–25. doi:10.1007/s10787-007-0021-x. PMID 18523733. S2CID 808858.
- Berners-Price SJ, Filipovska A (September 2011). “Gold compounds as therapeutic agents for human diseases”. Metallomics. 3 (9): 863–73. doi:10.1039/c1mt00062d. PMID 21755088.
- Tuure L, Hämäläinen M, Moilanen T, Moilanen E (2014). “Aurothiomalate inhibits the expression of mPGES-1 in primary human chondrocytes”. Scandinavian Journal of Rheumatology. 44 (1): 74–9. doi:10.3109/03009742.2014.927917. PMID 25314295. S2CID 5213201.
References
- Bieth JG (2001). “[The elastases]”. J. Soc. Biol. (in French). 195 (2): 173–9. doi:10.1051/jbio/2001195020173. PMID 11723830.
- Bruce, Alberts (2014-11-18). Molecular biology of the cell (Sixth ed.). New York, NY. ISBN 9780815344322. OCLC 887605755.
- Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC (1999). “Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis”. Nat. Genet. 23 (4): 433–6. doi:10.1038/70544. PMID 10581030. S2CID 6951666.
