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克洛素

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Klotho
識別號
别名;KL、​klotho、​uniprot:Q9UEF7
外部IDGeneCards[1]
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

n/a

n/a

蛋白序列

n/a

n/a

基因位置​(UCSC)n/an/a
PubMed​查找n/an/a
維基數據
檢視/編輯 人類

克洛素(Klotho)是一種由人類KL基因編碼而成的酵素[1]

該基因屬於第一型跨膜蛋白,且具有β-葡萄糖醛酸苷酶英语beta-glucuronidase活性。慢性腎衰竭患者體內的可羅素製造會減少,這也可能是造成慢性腎衰後一連串併發症的原因(如動脈硬化、骨質疏鬆、以及皮膚鬆弛等等)。該編碼基因的突變也與老化、骨質流失有關[2][3]。過度表現可羅素的小鼠,壽命會較野生型小鼠長[4]


功能[编辑]

克洛素為一種跨膜蛋白,會調控生物體對於胰島素的敏感性,且可能也與老化有關。本蛋白最早由黑尾誠等人於1997年發現[5],該蛋白命名自希腊神话命運三女神中的克洛托(Klotho)。

克洛素具有β-葡萄糖醛酸苷酶英语beta-glucuronidase活性,可以水解β-葡萄糖醛酸英语glucuronide,與人類老化有關[6][7]血漿中的循環克洛素會隨年紀逐漸減少[8]。β-克洛素會與FGF受體行程協同受體英语co-receptor,可與FGF19、FGF20、FGF23等成纤维细胞生长因子(FGF)結合進行作用[9][10]

克洛素缺乏的小鼠會出現類似人類早衰的症狀,並加速动脉血管硬化的進程,同時也會損傷血管新生內皮調控血管擴張的能力。推論克洛素可能可以透過內皮源性一氧化氮釋放來保護心血管系統。

過度表現克洛素的小鼠,平均壽命會較一般小數多出19%至31%[4]。克洛速基因的某些變異還與長壽和增進認知功能相關[11]

克洛素的作用機轉迄今未明,目前已知可以透過提升TRPV5英语TRPV5和降低TRPC6英语TRPC6的表達調控細胞的鈣平衡[12]。此外,克洛素也會增加內向整流離子通道ROMK英语ROMK的表達[12]。克洛素缺乏的小鼠會會增加維他命D的製造[13][14][15][16]

參考文獻[编辑]

  1. ^ Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochemical and Biophysical Research Communications. Jan 1998, 242 (3): 626–30. PMID 9464267. doi:10.1006/bbrc.1997.8019. 
  2. ^ Entrez Gene: klotho. 
  3. ^ Schumann G, Liu C, O'Reilly P, Gao H, Song P, Xu B, 等. KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. Proceedings of the National Academy of Sciences of the United States of America. 2016, 113 (50): 14372–14377. PMC 5167198. PMID 27911795. doi:10.1073/pnas.1611243113. 
  4. ^ 4.0 4.1 Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M. Suppression of aging in mice by the hormone Klotho. Science. Sep 2005, 309 (5742): 1829–33. Bibcode:2005Sci...309.1829K. PMC 2536606. PMID 16123266. doi:10.1126/science.1112766. 
  5. ^ Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. Nov 1997, 390 (6655): 45–51. Bibcode:1997Natur.390...45K. PMID 9363890. doi:10.1038/36285. 
  6. ^ Arking DE, Krebsova A, Macek M, Macek M, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. Association of human aging with a functional variant of klotho. Proceedings of the National Academy of Sciences of the United States of America. Jan 2002, 99 (2): 856–61. Bibcode:2002PNAS...99..856A. PMC 117395. PMID 11792841. doi:10.1073/pnas.022484299. 
  7. ^ Rodriguez T. Identifying significant biological markers in Klotho gene variants across wide ranging taxonomy. Journal of Molecular Biology Research. 2015, 5 (1): 11. doi:10.5539/jmbr.v5n1p11. 
  8. ^ Xiao NM, Zhang YM, Zheng Q, Gu J. Klotho is a serum factor related to human aging. Chinese Medical Journal. May 2004, 117 (5): 742–7. PMID 15161545. [永久失效連結]
  9. ^ Helsten T, Schwaederle M, Kurzrock R. Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications. Cancer Metastasis Reviews. 2015, 34 (3): 479–96. PMC 4573649. PMID 26224133. doi:10.1007/s10555-015-9579-8. 
  10. ^ Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA. FGF21 Regulates Sweet and Alcohol Preference. Cell Metabolism. February 2016, 23 (2): 344–9. PMC 4749404. PMID 26724861. doi:10.1016/j.cmet.2015.12.008. 
  11. ^ Dena B. Dubal et al., Life Extension Factor Klotho Enhances Cognition, Cell Reports, 2014, DOI: 10.1016/j.celrep.2014.03.076 (open access)
  12. ^ 12.0 12.1 Huang CL. Regulation of ion channels by secreted Klotho: mechanisms and implications. Kidney International. May 2010, 77 (10): 855–60. PMID 20375979. doi:10.1038/ki.2010.73. 
  13. ^ Kuro-o M. Klotho and aging. Biochimica et Biophysica Acta. Oct 2009, 1790 (10): 1049–58. PMC 2743784. PMID 19230844. doi:10.1016/j.bbagen.2009.02.005. 
  14. ^ Medici D, Razzaque MS, Deluca S, Rector TL, Hou B, Kang K, Goetz R, Mohammadi M, Kuro-O M, Olsen BR, Lanske B. FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis. The Journal of Cell Biology. Aug 2008, 182 (3): 459–65. PMC 2500132. PMID 18678710. doi:10.1083/jcb.200803024. 
  15. ^ Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Molecular Endocrinology. Dec 2003, 17 (12): 2393–403. PMID 14528024. doi:10.1210/me.2003-0048. 
  16. ^ Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T, Nabeshima Y. alpha-Klotho as a regulator of calcium homeostasis. Science. Jun 2007, 316 (5831): 1615–8. Bibcode:2007Sci...316.1615I. PMID 17569864. doi:10.1126/science.1135901. 

延伸閱讀[编辑]

外部連結[编辑]


克洛素引用了美国国家医学图书馆提供的資料,这些資料属于公共领域