胱抑素C

维基百科，自由的百科全书
维基百科中的医学内容仅供参考，并不能视作专业意见。如需获取医疗帮助或意见，请咨询专业人士。详见医学声明。
血清胱抑素C
(Cystatin C)
PDB的解译基于3gax[1].
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 CST3; ARMD11
扩展标识 遗传学：604312 鼠基因：102519 同源基因：78 ChEMBL: 1741304 GeneCards: CST3 Gene
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 1471 13010
Ensembl ENSG00000101439 ENSMUSG00000027447
UniProt P01034 P21460
mRNA序列 NM_000099 NM_009976
蛋白序列 NP_000090 NP_034106
基因位置 Chr 20:
23.61 – 23.62 Mb		 Chr 2:
148.87 – 148.88 Mb
PubMed查询 [1] [2]


胱抑素C(cystatin C、cystatin 3、gamma trace、血清胱抑素C、半胱氨酸蛋白酶抑制剂、胱蛋白、后γ-球蛋白，或神经内分泌基本多肽)，[2]是由CST3基因编码的一种蛋白质，其分子量小(13000)由体内有核细胞恒定产生，能自由通过(滤过)肾小球，且肾小管上皮细胞不分泌亦不重吸收，主要用作肾功能的生物标记。最近，已经研究了其在预测新发或恶化的心血管疾病的作用。它也似乎涉及类淀粉蛋白(一种特定类型的蛋白沉积)的脑功能障碍，如阿兹海默病。在人类中，所有细胞与细胞核(含DNA的细胞芯)产生具有120个氨基酸肽之血清胱抑素C。它几乎存在于所有的组织及体液中。它是一种溶酶体蛋白酶的酶抑制剂(来自于分解蛋白质的特定细胞亚单位的一种酶)，及可能是一种最重要的半胱氨酸蛋白酶(Cysteine protease)细胞外的(Extracellular)的抑制剂(经由的特定类型蛋白质降解酶、它可以防止细胞外蛋白质分解)。血清胱抑素C属于基因家族2型胱抑素(Cystatin)。

医学上的作用

肾的功能

参见：肾功能

肾小球滤过率(GFR)、肾脏健康标记物，最好是经由注入如菊粉、放射性同位素如51Cr-EDTA、125I-碘酞酸盐、99mTc-DTPA(pentetic acid)或造影剂如碘海醇(iohexol)等化合物测定，但这些技术有些复杂、昂贵、耗时且具有潜在的副作用。[3][4]肌酸酐是肾功能最广泛使用的生物标记。这在检测轻度肾功能损害是不准确的，并且检测水平会因肌肉质量及蛋白质的摄入量而有所不同。[5]公式如"克罗夫特-高尔特公式"及"肾病饮食改进(MDRD)公式"(参见肾功能)试着调整这些变量。

半胱氨酸蛋白酶抑制剂C具有低分子量(约13.3千道尔顿)，它是由血流在经由肾脏肾小球滤过而移除出来。如果肾功能和肾小球滤过率下降，胱抑素C血液水平升高。比起血清肌酸酐水平、血清胱抑素C的血清水平是肾功能(如肾小球滤过率、以GFR表示)的一个更精确的测试。[4][6]这一发现主要是基于横断面研究(Cross-sectional study)(在一单一的时间点)。纵向研究(Longitudinal study)(随时间的推移追踪血清胱抑素C)比较少；一些研究表明为有前景的成果。[7][8][9]相比于肌酸酐、血清胱抑素C的水平较少依赖年龄、性别、种族及肌肉质量等参数。单独的血清胱抑素C的测量还没有被证明优于肾功能的调整估计公式。[10]相对于之前的声称，血清胱抑素C已被发现受到身体组成的影响。[11][12]据认为，胱抑素C可以预测发展中的慢性肾脏病之风险，从而标示出"临床"肾功能不全的状态。[13]

研究还调查了胱抑素C作为肾功能药物剂量调整的标志。[14][15]

血清胱抑素C水平据报导会因患者致癌、[16][17][18](甚至轻微的)甲状腺功能障碍[19][20][21]及一些糖皮质激素的疗法[22][23]但并非所有的情况[24]而有所改变。其它的报告已经发现，其水平受到吸烟及C反应蛋白水平的影响。[25]在感染艾滋病毒时水平似乎在增加，这可能会或可能不会反映实际的肾功能不全。[26][27][28]在怀孕期间胱抑素C监测GFR的作用仍存在着争议。[29][30]如肌酸酐一样，胱抑素C的消除经由除使肾脏增加GFR的恶化外的路径。[31]

死亡及心血管疾病

肾功能不全会增加死亡和心血管疾病的风险。[32][33] 因为血清胱抑素C长期预后的结果已经出现可能比预期的GFR更强，已经假设血清胱抑素C也可能连接到独立肾功能的一种死亡率方式。[34]为符合自我管里的基因特性，已经表明半血清胱抑素C可能由基础代谢率所影响。[35]

神经系统疾病

这条件继承了显性(Dominance (genetics))的方式。

因为血清胱抑素C还结合β淀粉样蛋白(Amyloid beta)并降低其聚集及沉积，它是阿兹海默病的潜在目标。[36][37]据报导血清胱抑素C水平在阿兹海默病病患上显得较高。[38]

血清胱抑素C在多发性硬化症(Multiple sclerosis (MS))及其它脱髓鞘症(demyelinating disease)(其病征在髓鞘神经鞘的病损)的作用仍有争议。[39]

其他功用

血清胱抑素C水平降低动脉粥样硬化(所谓的动脉硬化)及主动脉的动脉瘤(aneurysm)(囊状膨出)病变。[40][41][42][43]

实验室测试

血清胱抑素C可使用免疫测定(immunoassay)法、如浊度计(nephelometer)或颗粒增强比浊法(turbidimetry)进行血清(其中的红血球和凝血因子已被去除之血液流体)的随机样本测定。[44]

在众多的人口里因性别与年龄，而有不同的参考值。

分子生物学

血清胱抑素C超级家族包括包含多个胱抑素样序列的蛋白质。

血清胱抑素C为一种非糖基化，碱性蛋白质(等电点在pH9.3)。

历史

血清胱抑素C最早于1961年在肾功能衰竭患者的尿液及脑脊液里被描述为"γ-轨迹"连同其它的轨迹(例如β-轨迹)作为一种微量蛋白。[45]格拉布(Grubb)与洛夫柏格(Löfberg)首次报导其氨基酸序列。[45]他们注意到晚期肾功能衰竭病患增加。[46]1985年由格拉布及其同事第一次提出作为肾小球滤过率的量测方法。[47][48]

根据2012年7月5日新英格兰医学杂志的一篇研究报告指出利用血清肌酸酐和胱抑素C被发现可以非常有效精确地反映GFR值。

参见

注释

  1. ^ Robert Kolodziejczyk, Karolina Michalska, Alejandra Hernandez-Santoyo, Maria Wahlbom, Anders Grubb, Mariusz Jaskolski. Crystal structure of human cystatin C stabilized against amyloid formation. The FEBS journal. 2010-04, 277 (7): 1726–1737 [2019-05-26]. ISSN 1742-4658. PMID 20175878. doi:10.1111/j.1742-4658.2010.07596.x. 
  2. ^ Alzforum: AlzGene. （原始内容存档于2004-12-27）. 
  3. ^ Zahran A, El-Husseini A, Shoker A. Can cystatin C replace creatinine to estimate glomerular filtration rate? A literature review. Am. J. Nephrol. 2007, 27 (2): 197–205 [2015-06-03]. PMID 17361076. doi:10.1159/000100907. （原始内容存档于2012-09-28）. 
  4. ^ 4.0 4.1 Roos JF, Doust J, Tett SE, Kirkpatrick CM. Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children--a meta-analysis. Clin. Biochem. March 2007, 40 (5–6): 383–391. PMID 17316593. doi:10.1016/j.clinbiochem.2006.10.026. 
  5. ^ King AJ, Levey AS. Dietary protein and renal function. J. Am. Soc. Nephrol. May 1993, 3 (11): 1723–37 [2015-06-03]. PMID 8329667. （原始内容存档于2023-04-07）. 
  6. ^ Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am. J. Kidney Dis. August 2002, 40 (2): 221–226 [2015-06-03]. PMID 12148093. doi:10.1053/ajkd.2002.34487. （原始内容存档于2022-09-09）. 
  7. ^ Premaratne E, MacIsaac RJ, Finch S, Panagiotopoulos S, Ekinci E, Jerums G. Serial measurements of cystatin C are more accurate than creatinine-based methods in detecting declining renal function in type 1 diabetes. Diabetes Care. May 2008, 31 (5): 971–973 [2015-06-03]. PMID 18319326. doi:10.2337/dc07-1588. （原始内容存档于2013-04-14）. 
  8. ^ Perkins BA; Nelson RG; Ostrander BE; et al. Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study. J. Am. Soc. Nephrol. May 2005, 16 (5): 1404–1412. PMC 2429917 可免费查阅. PMID 15788478. doi:10.1681/ASN.2004100854.  已忽略未知参数|author-separator= (帮助)
  9. ^ Corrao AM; Lisi G; Di Pasqua G; et al. Serum cystatin C as a reliable marker of changes in glomerular filtration rate in children with urinary tract malformations. J. Urol. January 2006, 175 (1): 303–309. PMID 16406933. doi:10.1016/S0022-5347(05)00015-7.  已忽略未知参数|author-separator= (帮助)
  10. ^ Stevens LA; Coresh J; Schmid CH; et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am. J. Kidney Dis. March 2008, 51 (3): 395–406 [2015-06-03]. PMC 2390827 可免费查阅. PMID 18295055. doi:10.1053/j.ajkd.2007.11.018. （原始内容存档于2020-09-26）.  已忽略未知参数|author-separator= (帮助)
  11. ^ Shlipak MG. Cystatin C as a marker of glomerular filtration rate in chronic kidney disease: influence of body composition. Nat Clin Pract Nephrol. April 2007, 3 (4): 188–189. PMID 17290239. doi:10.1038/ncpneph0404. 
  12. ^ Macdonald J; Marcora S; Jibani M; et al. GFR estimation using cystatin C is not independent of body composition. Am. J. Kidney Dis. November 2006, 48 (5): 712–719 [2015-06-03]. PMID 17059990. doi:10.1053/j.ajkd.2006.07.001. （原始内容存档于2018-09-12）.  已忽略未知参数|author-separator= (帮助)
  13. ^ Shlipak MG; Katz R; Sarnak MJ; et al. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Annals of Internal Medicine. August 2006, 145 (4): 237–46 [2015-06-03]. PMID 16908914. doi:10.7326/0003-4819-145-4-200608150-00003. （原始内容存档于2012-09-11）.  已忽略未知参数|author-separator= (帮助)
  14. ^ Hermida J, Tutor JC. Serum cystatin C for the prediction of glomerular filtration rate with regard to the dose adjustment of amikacin, gentamicin, tobramycin, and vancomycin. Ther Drug Monit. June 2006, 28 (3): 326–331 [2015-06-03]. PMID 16778715. doi:10.1097/01.ftd.0000211805.89440.3d. （原始内容存档于2016-01-20）. 
  15. ^ Schück O, Teplan V, Sibová J, Stollová M. Predicting the glomerular filtration rate from serum creatinine, serum cystatin C and the Cockcroft and Gault formula with regard to drug dosage adjustment. Int J Clin Pharmacol Ther. February 2004, 42 (2): 93–7. PMID 15180169. doi:10.5414/cpp42093. 
  16. ^ Demirtaş S, Akan O, Can M, Elmali E, Akan H. Cystatin C can be affected by nonrenal factors: a preliminary study on leukemia. Clin. Biochem. February 2006, 39 (2): 115–118. PMID 16337174. doi:10.1016/j.clinbiochem.2005.10.009. 
  17. ^ Nakai K; Kikuchi M; Fujimoto K; et al. Serum levels of cystatin C in patients with malignancy. Clin. Exp. Nephrol. April 2008, 12 (2): 132–139. PMID 18317874. doi:10.1007/s10157-008-0043-8.  已忽略未知参数|author-separator= (帮助)
  18. ^ Kos J, Stabuc B, Cimerman N, Brünner N. Serum cystatin C, a new marker of glomerular filtration rate, is increased during malignant progression. Clin. Chem. December 1998, 44 (12): 2556–7. PMID 9836733. [永久失效链接]
  19. ^ Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C. Impact of thyroid dysfunction on serum cystatin C. Kidney Int. May 2003, 63 (5): 1944–1947. PMID 12675875. doi:10.1046/j.1523-1755.2003.00925.x. 
  20. ^ Manetti L; Pardini E; Genovesi M; et al. Thyroid function differently affects serum cystatin C and creatinine concentrations. J. Endocrinol. Invest. April 2005, 28 (4): 346–9 [2015-06-03]. PMID 15966508. doi:10.1007/bf03347201. （原始内容存档于2008-06-08）.  已忽略未知参数|author-separator= (帮助)
  21. ^ Wiesli P, Schwegler B, Spinas GA, Schmid C. Serum cystatin C is sensitive to small changes in thyroid function. Clin. Chim. Acta. December 2003, 338 (1–2): 87–90 [2015-06-03]. PMID 14637271. doi:10.1016/j.cccn.2003.07.022. （原始内容存档于2018-06-08）. 
  22. ^ Risch L, Herklotz R, Blumberg A, Huber AR. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin. Chem. November 2001, 47 (11): 2055–9. PMID 11673383. [永久失效链接]
  23. ^ Cimerman N, Brguljan PM, Krasovec M, Suskovic S, Kos J. Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin. Chim. Acta. October 2000, 300 (1–2): 83–95. PMID 10958865. doi:10.1016/S0009-8981(00)00298-9. 
  24. ^ Bökenkamp A, van Wijk JA, Lentze MJ, Stoffel-Wagner B. Effect of corticosteroid therapy on serum cystatin C and beta2-microglobulin concentrations. Clin. Chem. July 2002, 48 (7): 1123–6. PMID 12089191. [永久失效链接]
  25. ^ Knight EL; Verhave JC; Spiegelman D; et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int. April 2004, 65 (4): 1416–1421. PMID 15086483. doi:10.1111/j.1523-1755.2004.00517.x.  已忽略未知参数|author-separator= (帮助)
  26. ^ Odden MC; Scherzer R; Bacchetti P; et al. Cystatin C level as a marker of kidney function in human immunodeficiency virus infection: the FRAM study. Arch. Intern. Med. November 2007, 167 (20): 2213–2219 [2015-06-03]. PMC 3189482 可免费查阅. PMID 17998494. doi:10.1001/archinte.167.20.2213. （原始内容存档于2008-06-07）.  已忽略未知参数|author-separator= (帮助)
  27. ^ Collé A; Tavera C; Prévot D; et al. Cystatin C levels in sera of patients with human immunodeficiency virus infection. A new avidin-biotin ELISA assay for its measurement. J Immunoassay. 1992, 13 (1): 47–60. PMID 1569212. doi:10.1080/15321819208019824.  已忽略未知参数|author-separator= (帮助)
  28. ^ Jaroszewicz J, Wiercinska-Drapalo A, Lapinski TW, Prokopowicz D, Rogalska M, Parfieniuk A. Does HAART improve renal function? An association between serum cystatin C concentration, HIV viral load and HAART duration. Antivir. Ther. (Lond.). 2006, 11 (5): 641–5. PMID 16964834. 
  29. ^ Strevens H, Wide-Swensson D, Torffvit O, Grubb A. Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy. Scand. J. Clin. Lab. Invest. 2002, 62 (2): 141–147. PMID 12004930. doi:10.1080/003655102753611771. 
  30. ^ Akbari A; Lepage N; Keely E; et al. Cystatin-C and beta trace protein as markers of renal function in pregnancy. BJOG. May 2005, 112 (5): 575–578. PMID 15842279. doi:10.1111/j.1471-0528.2004.00492.x.  已忽略未知参数|author-separator= (帮助)
  31. ^ Sjöström P, Tidman M, Jones I. Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand. J. Clin. Lab. Invest. 2005, 65 (2): 111–124. PMID 16025834. doi:10.1080/00365510510013523. 
  32. ^ Tonelli M; Wiebe N; Culleton B; et al. Chronic kidney disease and mortality risk: a systematic review. J. Am. Soc. Nephrol. July 2006, 17 (7): 2034–2047. PMID 16738019. doi:10.1681/ASN.2005101085.  已忽略未知参数|author-separator= (帮助)
  33. ^ Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. September 2004, 351 (13): 1296–1305. PMID 15385656. doi:10.1056/NEJMoa041031. 
  34. ^ Stevens LA, Levey AS. Chronic kidney disease in the elderly--how to assess risk. N. Engl. J. Med. May 2005, 352 (20): 2122–2124. PMID 15901867. doi:10.1056/NEJMe058035. 
  35. ^ Delanaye P, Cavalier E, Krzesinski JM. Cystatin C, renal function, and cardiovascular risk. Annals of Internal Medicine. February 2008, 148 (4): 323. PMID 18283218. doi:10.7326/0003-4819-148-4-200802190-00023. 
  36. ^ Mi W; Pawlik M; Sastre M; et al. Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models. Nat. Genet. December 2007, 39 (12): 1440–1442. PMID 18026100. doi:10.1038/ng.2007.29.  已忽略未知参数|author-separator= (帮助)
  37. ^ Kaeser SA; Herzig MC; Coomaraswamy J; et al. Cystatin C modulates cerebral beta-amyloidosis. Nat. Genet. December 2007, 39 (12): 1437–1439. PMID 18026102. doi:10.1038/ng.2007.23.  已忽略未知参数|author-separator= (帮助)
  38. ^ Chuo LJ, Sheu WH, Pai MC, Kuo YM. Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease. Dement Geriatr Cogn Disord. 2007, 23 (4): 251–257 [2015-06-03]. PMID 17310123. doi:10.1159/000100021. （原始内容存档于2012-09-28）. 
  39. ^ Del Boccio P; Pieragostino D; Lugaresi A; et al. Cleavage of cystatin C is not associated with multiple sclerosis. Annals of Neurology. August 2007, 62 (2): 201–204. PMID 17006926. doi:10.1002/ana.20968.  已忽略未知参数|author-separator= (帮助)
  40. ^ Shi GP; Sukhova GK; Grubb A; et al. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J. Clin. Invest. November 1999, 104 (9): 1191–1197. PMC 409823 可免费查阅. PMID 10545518. doi:10.1172/JCI7709.  已忽略未知参数|author-separator= (帮助)
  41. ^ Abisi S, Burnand KG, Waltham M, Humphries J, Taylor PR, Smith A. Cysteine protease activity in the wall of abdominal aortic aneurysms. J. Vasc. Surg. December 2007, 46 (6): 1260–1266 [2015-06-03]. PMID 18155003. doi:10.1016/j.jvs.2007.08.015. （原始内容存档于2018-11-04）. 
  42. ^ Abdul-Hussien H; Soekhoe RG; Weber E; et al. Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases (– Scholar search). Am. J. Pathol. March 2007, 170 (3): 809–817. PMC 1864891 可免费查阅. PMID 17322367. doi:10.2353/ajpath.2007.060522.  已忽略未知参数|author-separator= (帮助) [失效链接]
  43. ^ Gacko M, Chyczewski L, Chrostek L. Distribution, activity and concentration of cathepsin B and cystatin C in the wall of aortic aneurysm. Pol J Pathol. 1999, 50 (2): 83–6. PMID 10481531. 
  44. ^ Croda-Todd MT, Soto-Montano XJ, Hernández-Cancino PA, Juárez-Aguilar E. Adult cystatin C reference intervals determined by nephelometric immunoassay. Clin. Biochem. September 2007, 40 (13–14): 1084–1087 [2015-06-03]. PMID 17624320. doi:10.1016/j.clinbiochem.2007.05.011. （原始内容存档于2018-01-29）. 
  45. ^ 45.0 45.1 Grubb A, Löfberg H. Human gamma-trace, a basic microprotein: amino acid sequence and presence in the adenohypophysis. Proc. Natl. Acad. Sci. U.S.A. May 1982, 79 (9): 3024–3027. PMC 346341 可免费查阅. PMID 6283552. doi:10.1073/pnas.79.9.3024. 
  46. ^ Löfberg H, Grubb AO. Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system. Scand. J. Clin. Lab. Invest. November 1979, 39 (7): 619–626. PMID 119302. doi:10.3109/00365517909108866. 
  47. ^ Grubb A, Simonsen O, Sturfelt G, Truedsson L, Thysell H. Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate. Acta Med Scand. 1985, 218 (5): 499–503. PMID 3911736. doi:10.1111/j.0954-6820.1985.tb08880.x. 
  48. ^ Simonsen O, Grubb A, Thysell H. The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate. Scand. J. Clin. Lab. Invest. April 1985, 45 (2): 97–101. PMID 3923607. doi:10.3109/00365518509160980. 

外部链接

常见淀粉样蛋白形成的蛋白质
系统性淀粉样变
器官局限性类淀粉样变
取自“https://zh.wikipedia.org/w/index.php?title=胱抑素C&oldid=79072360”