胱天蛋白酶12
胱天蛋白酶12（英語：Caspase 12）是人類中由CASP12基因編碼的蛋白質。該蛋白質屬於胱天蛋白酶家族，可在C端天門冬胺酸殘基處裂解其受質。它與胱天蛋白酶1和胱天蛋白酶家族的其他成員密切相關。它們被稱為炎性胱天蛋白酶，這些酶處理並活化炎性細胞因子，如白血球介素1和白血球介素18。
基因
[編輯]該酶位於人類11號染色體上，與其他炎性胱天蛋白酶位於同一位點。[6]許多可獲得完整基因組資料的哺乳動物都已鑑定出CASP12直系同源物。[7]
臨床意義
[編輯]CASP12基因存在多態性，可以生成完整的胱天蛋白酶（Csp12L）或無活性的截短形式（Csp12S）。該功能形式似乎僅存在於非洲人後裔，並且與敗血症的易感性有關。攜帶該功能基因的人對脂多醣（LPS）等細菌分子的反應會減弱。[8][9]
麥吉爾大學健康中心於2009年5月的一項研究表明，雌激素可能會阻止胱天蛋白酶12的產生，從而導致對細菌病原體產生更強的發炎反應。該試驗是在植入了人類胱天蛋白酶12基因的實驗小鼠身上進行的。[10][11][12]
大約60至10萬年前開始的正選擇，CASP12基因的非活性截短形式（Csp12S）在非非洲人群中傳播並幾乎是固定的。它的選擇性優勢被認為是體現為隨著人口規模和密度的增加而經歷更多傳染病的人群對敗血症的抵抗力。[13][14]
參考文獻
[編輯]- ^ 對Caspase 12 (gene/pseudogene)起作用的藥物；在維基數據上查看/編輯參考.
- ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000204403 - Ensembl, May 2017
- ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000025887 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Fischer H, Koenig U, Eckhart L, Tschachler E. Human caspase 12 has acquired deleterious mutations. Biochem. Biophys. Res. Commun. 2002, 293 (2): 722–6. PMID 12054529. doi:10.1016/S0006-291X(02)00289-9.
- ^ OrthoMaM phylogenetic marker: CASP12 coding sequence.[永久失效連結]
- ^ Saleh M, Vaillancourt JP, Graham RK, Huyck M, Srinivasula SM, Alnemri ES, Steinberg MH, Nolan V, Baldwin CT, Hotchkiss RS, Buchman TG, Zehnbauer BA, Hayden MR, Farrer LA, Roy S, Nicholson DW. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature. 2004, 429 (6987): 75–9. Bibcode:2004Natur.429...75S. PMID 15129283. doi:10.1038/nature02451
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- ^ Saleh, Maya Mathison; John C. Wolinski; Melissa K. Bensinger; Steve J. Fitzgerald; Patrick Droin; Nathalie Ulevitch; Richard J. Green; Douglas R. Nicholson; Donald W. Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature. 2006, 440 (7087): 1064–1068. Bibcode:2006Natur.440.1064S. PMID 16625199. S2CID 4321520. doi:10.1038/nature04656.
- ^ Yeretssian G, Doiron K, Shao W, Leavitt BR, Hayden MR, Nicholson DW, Saleh M. Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection. Proc. Natl. Acad. Sci. U.S.A. May 2009, 106 (22): 9016–20. Bibcode:2009PNAS..106.9016Y. PMC 2690057 . PMID 19447924. doi:10.1073/pnas.0813362106 .
- ^ Man flu: real or myth?. Health. NHS UK. 2009-05-18 [23 May 2009]. （原始內容存檔於16 February 2010）.
- ^ Women 'fight off disease better'. Health. BBC News. 2009-05-13 [2009-05-13]. （原始內容存檔於2023-03-08）.
- ^ Xue, Yali; Daly, Allan; Yngvadottir, Bryndis; Liu, Mengning; Coop, Graham; Kim, Yuseob; Sabeti, Pardis; Chen, Yuan; Stalker, Jim; Huckle, Elizabeth; Burton, John; Leonard, Steven; Rogers, Jane; Tyler-Smith, Chris. Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection. The American Journal of Human Genetics. 2006, 78 (4): 659–670. PMC 1424700 . PMID 16532395. doi:10.1086/503116.
- ^ Wang, Xiaoxia; Grus, Wendy E.; Zhang, Jianzhi. Gene Losses during Human Origins. PLOS Biology. 2006, 4 (3): e52. PMC 1361800 . PMID 16464126. doi:10.1371/journal.pbio.0040052 .
