Changes of proteins induced by anticoagulants can be more sensitively detected in urine than in plasma

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英文篇名：Changes of proteins induced by anticoagulants can be more sensitively detected in urine than in plasma 作者：LI ; MengLin ; ZHAO ; MinDi ; GAO ; YouHe 英文作者：LI MengLin;ZHAO MinDi;GAO YouHe;National Key Laboratory of Medical Molecular Biology,Department of Physiology and Pathophysiology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College; 英文关键词：biomarker,homeostasis,urine,plasma,proteomics 中文刊名：JCXG 英文刊名：中国科学:生命科学(英文版) 机构：National Key Laboratory of Medical Molecular Biology,Department of Physiology and Pathophysiology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College; 出版日期：2014-07-05 出版单位：Science China(Life Sciences) 年：2014 期：v.57 基金：supported by the National Basic Research Program of China (2012CB517606,2013CB530805);; Expertise-Introduction Project for Disciplinary Innovation of Universities (B08007);; National Natural Science Foundation of China (31200614);; Beijing Natural Science Foundation (5132028) 语种：英文; 页：JCXG201407002 页数：10 CN：07 ISSN：11-5841/Q 分类号：9-18

摘要

The most fundamental property of biomarkers is change.But changes are hard to maintain in plasma since it is strictly controlled by homeostatic mechanisms of the body.There is no homeostatic mechanism for urine.Besides,urine is partly a filtration of blood,and systematic information can be reflected in urine.We hypothesize that change of blood can be reflected in urine more sensitively.Here we introduce the interference into the blood by two anticoagulants heparin or argatroban.Plasma and urine proteins were profiled by LC-MS/MS and then validated by Western blot in totally six SD female rats before and after the drug treatments.In argatroban treated group,with exactly the same experimental procedure and the same cutoff value for both plasma and urine proteins,62 proteins changed in urine,only one of which changed in plasma.In heparin treated group,27 proteins changed in urine but only three other proteins changed in plasma.Both LC-MS/MS and Western blot analyses demonstrated drug-induced increases in transferrin and hemopexin levels in urine but not in plasma.Our data indicates that urine may serve as a source for more sensitive detection of protein biomarkers than plasma.
        The most fundamental property of biomarkers is change.But changes are hard to maintain in plasma since it is strictly controlled by homeostatic mechanisms of the body.There is no homeostatic mechanism for urine.Besides,urine is partly a filtration of blood,and systematic information can be reflected in urine.We hypothesize that change of blood can be reflected in urine more sensitively.Here we introduce the interference into the blood by two anticoagulants heparin or argatroban.Plasma and urine proteins were profiled by LC-MS/MS and then validated by Western blot in totally six SD female rats before and after the drug treatments.In argatroban treated group,with exactly the same experimental procedure and the same cutoff value for both plasma and urine proteins,62 proteins changed in urine,only one of which changed in plasma.In heparin treated group,27 proteins changed in urine but only three other proteins changed in plasma.Both LC-MS/MS and Western blot analyses demonstrated drug-induced increases in transferrin and hemopexin levels in urine but not in plasma.Our data indicates that urine may serve as a source for more sensitive detection of protein biomarkers than plasma.

引文

1 Yi J,Kim C,Gelfand CA.Inhibition of intrinsic proteolytic activities moderates preanalytical variability and instability of human plasma.J Proteome Res,2007,6:1768–1781
    2 Decramer S,Gonzalez de Peredo A,Breuil B,Mischak H,Monsarrat B,Bascands JL,Schanstra JP.Urine in clinical proteomics.Mol Cell Proteomics,2008,7:1850–1862
    3 Omenn GS,States DJ,Adamski M,Blackwell TW,Menon R,Hermjakob H,Apweiler R,Haab BB,Simpson RJ,Eddes JS,Kapp EA,Moritz RL,Chan DW,Rai AJ,Admon A,Aebersold R,Eng J,Hancock WS,Hefta SA,Meyer H,Paik YK,Yoo JS,Ping P,Pounds J,Adkins J,Qian X,Wang R,Wasinger V,Wu CY,Zhao X,Zeng R,Archakov A,Tsugita A,Beer I,Pandey A,Pisano M,Andrews P,Tammen H,Speicher DW,Hanash SM.Overview of the hupo plasma proteome project:results from the pilot phase with 35 collaborating laboratories and multiple analytical groups,generating a core datasetof 3020 proteins and a publicly-available database.Proteomics,2005,5 :3226–3245
    4 Theodorescu D,Wittke S,Ross MM,Walden M,Conaway M,Just I,Mischak H,Frierson HF.Discovery and validation of new protein biomarkers for urothelial cancer:a prospective analysis.Lancet Oncol,2006,7:230–240
    5 Schaub S,Wilkins J,Weiler T,Sangster K,Rush D,Nickerson P.Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry.Kidney Int,2004,65:323 –332
    6 Jia L,Liu X,Liu L,Li M,Gao Y.Urimem,a membrane that can store urinary proteins simply and economically,makes the large-scale storage of clinical samples possible.Peer J PrePrints,2013,1:e37v31
    7 Gao Y.Urine—an untapped goldmine for biomarker discovery?Sci China Life Sci,2013,56:1145–1146
    8 Thongboonkerd V,McLeish KR,Arthur JM,Klein JB.Proteomic analysis of normal human urinary proteins isolated by acetone precipitation or ultracentrifugation.Kidney Int,2002,62:1461–1469
    9 Garcia-Manzano A,Gonzalez-Llaven J,Lemini C,Rubio-Poo C.Standardization of rat blood clotting tests with reagents used for humans.Proc West Pharmacol Soc,2001,44:153–155
    10 Wisniewski JR,Zougman A,Nagaraj N,Mann M.Universal sample preparation method for proteome analysis.Nat Methods,2009,6:359 –362
    11 Keller A,Nesvizhskii AI,Kolker E,Aebersold R.Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search.Anal Chem,2002,74:5383–5392
    12 Hauck SM,Dietter J,Kramer RL,Hofmaier F,Zipplies JK,Amann B,Feuchtinger A,Deeg CA,Ueffing M.Deciphering membraneassociated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry.Mol Cell Proteomics,2010,9:2292–2305
    13 Brunzel N.Fundamentals of Urine&Body Fluid Analysis.Philadelphia:Saunders,2004.480
    14 Pieper R,Gatlin CL,Makusky AJ,Russo PS,Schatz CR,Miller SS,Su Q,McGrath AM,Estock MA,Parmar PP,Zhao M,Huang ST,Zhou J,Wang F,Esquer-Blasco R,Anderson NL,Taylor J,Steiner S.The human serum proteome:display of nearly 3700 chromatographically separated protein spots on two-dimensional electrophoresis gels and identification of 325 distinct proteins.Proteomics,2003,3:1345–1364
    15 Nagaraj N,Mann M.Quantitative analysis of the intra-and inter-individual variability of the normal urinary proteome.J Proteome Res,2011,10:637–645
    16 Adkins JN,Varnum SM,Auberry KJ,Moore RJ,Angell NH,Smith RD,Springer DL,Pounds JG.Toward a human blood serum proteome:analysis by multidimensional separation coupled with mass spectrometry.Mol Cell Proteomics,2002,1:947–955
    17 Mehta AI,Ross S,Lowenthal MS,Fusaro V,Fishman DA,Petricoin EF,3rd,Liotta LA.Biomarker amplification by serum carrier protein binding.Dis Markers,2003,19:1–10
    18 Shen Y,Kim J,Strittmatter EF,Jacobs JM,Camp DG,2nd,Fang R,Tolie N,Moore RJ,Smith RD.Characterization of the human blood plasma proteome.Proteomics,2005,5:4034–4045
    19 Kentsis A,Monigatti F,Dorff K,Campagne F,Bachur R,Steen H.Urine proteomics for profiling of human disease using high accuracy mass spectrometry.Proteomics Clin Appl,2009,3:1052–1061
    20 Wang L,Li F,Sun W,Wu S,Wang X,Zhang L,Zheng D,Wang J,Gao Y.Concanavalin A-captured glycoproteins in healthy human urine.Mol Cell Proteomics,2006,5:560–562
    21 Sleat DE,Zheng H,Lobel P.The human urine mannose 6-phosphate glycoproteome.Biochim Biophys Acta,2007,1774:368–372
    22 Yang N,Feng S,Shedden K,Xie X,Liu Y,Rosser CJ,Lubman DM,Goodison S.Urinary glycoprotein biomarker discovery for bladder cancer detection using LC/MS-MS and label-free quantification.Clin Cancer Res,2011,17:3349–3359
    23 Halim A,Nilsson J,Rüetschi U,Hesse C,Larson G.Human urinary glycoproteomics;attachment site specific analysis of N-and O-linked glycosylations by CID and ECD.Mol Cell Proteomics,2012,11:M111.013649
    24 Khadjavi A,Barbero G,Destefanis P,Mandili G,Giribaldi G,Mannu F,Pantaleo A,Ceruti C,Bosio A,Rolle L,Turrini F,Fontana D.Evidence of abnormal tyrosine phosphorylated proteins in the urine of patients with bladder cancer:the road toward a new diagnostic tool?J Urol,2011,185:1922–1929
    25 Liu L,Liu X,Sun W,Li M,Gao Y.Unrestrictive identification of post-translational modifications in the urine proteome without enrichment.Proteome science,2013,11:1
    26 McDonald WH,Yates JR 3rd.Shotgun proteomics and biomarker discovery.Dis Markers,2002,18:99–105
    27 Chen T,Xie G,Wang X,Fan J,Qiu Y,Zheng X,Qi X,Cao Y,Su M,Wang X,Xu LX,Yen Y,Liu P,Jia W.Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma.Mol Cell Proteomics,2011,10:M110 004945
    28 Siwy J,Mullen W,Golovko I,Franke J,Zurbig P.Human urinary peptide database for multiple disease biomarker discovery.Proteomics Clin Appl,2011,5:367–374
    29 Nicholson JK,Wilson ID.Understanding‘global’systems biology:metabonomics and the continuum of metabolism.Nat Rev Drug Discov,2003,2:668–676
    30 Shao C,Li M,Li X,Wei L,Zhu L,Yang F,Jia L,Mu Y,Wang J,Guo Z,Zhang D,Yin J,Wang Z,Sun W,Zhang Z,Gao Y.A tool for biomarker discovery in the urinary proteome:a manually curated human and animal urine protein biomarker database.Mol Cell Proteomics,2011,10:M111 010975
    31 Wu T,Du Y,Han J,Singh S,Xie C,Guo Y,Zhou XJ,Ahn C,Saxena R,Mohan C.Urinary angiostatin—a novel putative marker of renal pathology chronicity in lupus nephritis.Mol Cell Proteomics,2013,12 :1170–1179
    32 Pories SE,Zurakowski D,Roy R,Lamb CC,Raza S,Exarhopoulos A,Scheib RG,Schumer S,Lenahan C,Borges V,Louis GW,Anand A,Isakovich N,Hirshfield-Bartek J,Wewer U,Lotz MM,Moses MA.Urinary metalloproteinases:noninvasive biomarkers for breast cancer risk assessment.Cancer Epidemiol Biomarkers Prev,2008,17:1034–1042
    33 Huang JT,Chaudhuri R,Albarbarawi O,Barton A,Grierson C,Rauchhaus P,Weir CJ,Messow M,Stevens N,McSharry C,Feuerstein G,Mukhopadhyay S,Brady J,Palmer CN,Miller D,Thomson NC.Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease.Thorax,2012,67 :502–508
    34 Thomas CE,Sexton W,Benson K,Sutphen R,Koomen J.Urine collection and processing for protein biomarker discovery and quantification.Cancer Epidemiol Biomarkers Prev,2010,19:953 –959
    35 Weissinger EM,Wittke S,Kaiser T,Haller H,Bartel S,Krebs R,Golovko I,Rupprecht HD,Haubitz M,Hecker H,Mischak H,Fliser D.Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes.Kidney Int,2004,65:2426–2434
    36 Jantos-Siwy J,Schiffer E,Brand K,Schumann G,Rossing K,Delles C,Mischak H,Metzger J.Quantitative urinary proteome analysis for biomarker evaluation in chronic kidney disease.J Proteome Res,2009,8:268–281
    37 Lankisch P,Wessalowski R,Maisonneuve P,Haghgu M,Hermsen D,Kramm CM.Serum cystatin C is a suitable marker for routine monitoring of renal function in pediatric cancer patients,especially of very young age.Pediatr Blood Cancer,2006,46:767–772
    38 Lemm G,Kuppers J,Frey R,Wingender W,Kuhlmann J.Monitoring of proteinuria in phase I studies in healthy male subjects.Eur J Clin Pharmacol,1998,54:287–294