Biology:Caspase 12
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Caspase 12 is a protein that in humans is encoded by the CASP12 gene. The protein belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18.
Gene
It is found on chromosome 11 in humans in a locus with other inflammatory caspases.[1] CASP12 orthologs[2] have been identified in numerous mammals for which complete genome data are available.
Clinical significance
The CASP12 gene is subject to polymorphism, which can generate a full-length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS).[3][4]
A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block the production of caspase-12, resulting in a stronger inflammatory reaction to bacterial pathogens. The trials were carried out on laboratory mice which had been implanted with the human caspase-12 gene.[5][6][7]
The inactive truncated form (Csp12S) of the CASP12 gene was spread and nearly fixed in non-African populations due to positive selection beginning perhaps 60–100 thousand years ago. Its selective advantage is thought to be sepsis resistance in populations that experienced more infectious diseases as population sizes and densities increased.[8][9]
References
- ↑ "Human caspase 12 has acquired deleterious mutations". Biochem. Biophys. Res. Commun. 293 (2): 722–6. 2002. doi:10.1016/S0006-291X(02)00289-9. PMID 12054529.
- ↑ "OrthoMaM phylogenetic marker: CASP12 coding sequence". http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000204403_CASP12.xml.[yes|permanent dead link|dead link}}]
- ↑ "Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms". Nature 429 (6987): 75–9. 2004. doi:10.1038/nature02451. PMID 15129283. Bibcode: 2004Natur.429...75S.
- ↑ Saleh, Maya Mathison; John C. Wolinski; Melissa K. Bensinger; Steve J. Fitzgerald; Patrick Droin; Nathalie Ulevitch; Richard J. Green; Douglas R. Nicholson et al. (2006). "Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice". Nature 440 (7087): 1064–1068. doi:10.1038/nature04656. PMID 16625199. Bibcode: 2006Natur.440.1064S.
- ↑ "Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection". Proc. Natl. Acad. Sci. U.S.A. 106 (22): 9016–20. May 2009. doi:10.1073/pnas.0813362106. PMID 19447924. Bibcode: 2009PNAS..106.9016Y.
- ↑ "Man flu: real or myth?". Health. NHS UK. 2009-05-18. http://www.nhs.uk/news/2009/05May/Pages/Manflurealormyth.aspx.
- ↑ "Women 'fight off disease better'". Health. BBC News. 2009-05-13. http://news.bbc.co.uk/1/hi/health/8047321.stm. Retrieved 2009-05-13.
- ↑ Xue, Yali; Daly, Allan; Yngvadottir, Bryndis; Liu, Mengning; Coop, Graham; Kim, Yuseob; Sabeti, Pardis; Chen, Yuan et al. (2006). "Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection". The American Journal of Human Genetics 78 (4): 659–670. doi:10.1086/503116. PMID 16532395.
- ↑ Wang, Xiaoxia; Grus, Wendy E.; Zhang, Jianzhi (2006). "Gene Losses during Human Origins". PLOS Biology 4 (3): e52. doi:10.1371/journal.pbio.0040052. PMID 16464126.
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