【產(chǎn)品名稱】
通用名稱:阿狄科®總α KLOTHO檢測(cè)試劑盒(酶聯(lián)免疫法)
英文名稱:IDK® total alpha-Klotho
【包裝規(guī)格】
96人份/盒
【預(yù)期用途】
用于測(cè)定血清中的 Klotho。
僅供科研使用。
【背景知識(shí)】
抗衰老蛋白 a-Klotho (KL) 調(diào)節(jié)鈣穩(wěn)態(tài)和磷酸鹽穩(wěn)態(tài),并顯示出與各種癌癥疾病的聯(lián)系。小鼠的缺陷導(dǎo)致的臨床特征與人類衰老缺陷中發(fā)現(xiàn)的相似。
Klotho 基因編碼 KL 蛋白,位于 13 號(hào)染色體上。它由 5 個(gè)外顯子和 4 個(gè)內(nèi)含子組成,大小為 50 kb。人類基因序列與小鼠基因序列對(duì)應(yīng)98%,而大鼠基因序列與人類基因序列僅對(duì)應(yīng)86%。
KL 存在三種變體:膜結(jié)合 KL、可溶性 KL 和分泌型 KL。所有三種 KL 變體都有一個(gè) N 端區(qū)域,用作信號(hào)肽結(jié)構(gòu)域。該信號(hào)序列由 33 個(gè)氨基酸組成,富含疏水性氨基酸并誘導(dǎo) KL 從胞質(zhì)溶膠易位至膜。目前尚無 KL 的翻譯后修飾。膜結(jié)合 KL 由 1012 個(gè)氨基酸(約 130 kDa)組成,由一個(gè)信號(hào)肽、兩個(gè)結(jié)構(gòu)域 KL1 和 KL2(每個(gè)約 65 kDa)和一個(gè) 29 個(gè)氨基酸長的跨膜結(jié)構(gòu)域組成。可溶性KL是通過分裂細(xì)胞膜產(chǎn)生的,分為兩種不同的裂解產(chǎn)物:a-cut和$-cut。a-cut描述了KL2結(jié)構(gòu)域和跨膜結(jié)構(gòu)域之間的界面,即所謂的可溶性KL a-cut 產(chǎn)物形成,它由結(jié)構(gòu)域 KL1 和 KL2 以及信號(hào)肽組成。另一個(gè)界面位于 KL1 和 KL2 結(jié)構(gòu)域之間,這會(huì)產(chǎn)生所謂的 B 切割產(chǎn)物,它僅由 KL1 結(jié)構(gòu)域和信號(hào)肽組成。兩種產(chǎn)品一起形成稱為可溶性 KL 的蛋白質(zhì)形式,可在血液中循環(huán),也可以在尿液中找到。分泌型 KL 由可變剪接形成,由信號(hào)肽和 KL1 組成,大小約為 65 kDa。分泌型 KL 與可溶性 B 切割 KL 的區(qū)別在于 C 末端有 15 個(gè)氨基酸長的序列。
該測(cè)試可檢測(cè)血清中的可溶性和分泌型 α-Klotho。
參考文獻(xiàn):
1. Rotondi, S. et al., 2015.Soluble a-Klotho Serum Levels in Chronic Kidney Disease.lnternational journal of endocrinology, 2015,p.872193.
2. Koizumi,M., Komaba,H. & Fukagawa,M.,2013.Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis. Contributions to nephrology,180,pp.110-23.
3. Shimamura, Y. et al.,2012.Serum levels of soluble secreted a-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel bio-marker for early diagnosis. Clinical and experimental nephrology,16(5), pp.722-9.
4. John,G.B., Cheng,C.-Y.& Kuro-o,M.,2011.Role of Klotho in aging, phosphate metabolism, and CKD.American journal of kidney diseases : the official journal ofthe National Kidney Foundation, 58(1),pp.127-34.
5. Kuro-o, M.,2008.Klotho as a regulator of oxidative stress and senescence.Biological chemistry, 389(3), pp.233-41.
6. Kuro-o, M.et al., 1997.Mutation of the mouse klotho gene leads to a syndrome resembling ageing.Nature, 390(6655), pp.45-51.
7. Hu, M.C., Kuro-o,M.& Moe, O.W.,2014.aKlotho and vascular calcification: an evolving paradigm. Current opinion in nephrology and hypertension, 23(4), pp.331-9.
8. Hu, M.C.et al.,2011.Klotho deficiency causes vascular calcification in chronic kidney disease.Journal of theAmerican Society of Nephrology :JASN, 22(1), pp.124-36.
9. Xu, Y.& Sun,Z.,2015. Molecular basis of Klotho: from gene to function in aging.
Endocrine reviews, 36(2), pp.174-93.
10.Martin-Nunez,E.et al,2014.lmplications of Klotho in vascular health and disease.World journal of cardiology,6(12), pp.1262-9.
11.Kitagawa, M.et al.,2013.A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidneydisease.K.Jandeleit-Dahm, ed.PloS one,8(2), p.e56695.
12.Silver,J.,Rodriguez, M.& Slatopolsky,E.,2012.FGF23 and PTH--double agents at the heart of CKD. Nephrology, dialysis, transplantation : official publication of theEuropean Dialysis and Transplant Association - European Renal Association, 27(5),pp.1715-20.
13.Hu, M.C.,Kuro-o,M.& Moe, O.W.,2013.Klotho and chronic kidney disease.Contributions to nephrology,180, pp.47-63.
14.Vervloet, M.G.et al.,2014.The role of klotho on vascular calcification and endothelial function in chronic kidney disease. Seminars in nephrology,34(6), pp.578-85.
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