Swan Erin E Leary, Peppi Marcello, Chen Zhiqiang, Green Karin M, Evans James E, McKenna Michael J, Mescher Mark J, Kujawa Sharon G, Sewell William F
Charles Stark Draper Laboratory, Cambridge, Massachusetts, USA.
Laryngoscope. 2009 May;119(5):953-8. doi: 10.1002/lary.20209.
Proteins in perilymph may alter the delivery profile of implantable intracochlear drug delivery systems through biofouling. Knowledge of protein composition will help anticipate interactions with delivered agents.
Analysis of mouse perilymph.
Protein composition of perilymph and cerebrospinal fluid (CSF) was analyzed using a capillary liquid chromatography-mass spectrometry-based iTRAQ quantitative proteomics approach. We searched against a mouse subset of the Uniprot FASTA protein database. We sampled perilymph from the apex of the mouse cochlea to minimize CSF contamination.
More than 50 explicit protein isoforms were identified with very high confidence. iTRAQ reporter ions allowed determination of relative molar amounts of proteins between perilymph and CSF. Protein in perilymph was almost three times more concentrated than in CSF. More than one-third of the proteins in perilymph comprised protease inhibitors, with serpins being the predominant group. Apolipoproteins constituted 16%. Fifteen percent of the proteins were enzymes. Albumin was the most abundant single protein (14%). Proteins with relatively high perilymph/CSF ratios included broad-spectrum protease inhibitors and apolipoproteins.
Some proteins found in perilymph, such as albumin and HMW kininogen, have been implicated in biofouling through adsorption to device materials. The relatively large quantities of apolipoprotein and albumin may serve as a reservoir for acidic and lipophilic drugs. Alpha-2-glycoprotein can bind basic drugs.
Perilymph is similar in protein composition to CSF, though amounts are 2.8 times higher. Protease inhibitors comprise the largest category of proteins.
外淋巴中的蛋白质可能通过生物污染改变植入式耳蜗给药系统的给药分布。了解蛋白质组成将有助于预测与给药药物的相互作用。
小鼠外淋巴分析。
采用基于毛细管液相色谱 - 质谱的iTRAQ定量蛋白质组学方法分析外淋巴和脑脊液（CSF）的蛋白质组成。我们在Uniprot FASTA蛋白质数据库的小鼠子集中进行搜索。我们从小鼠耳蜗顶端采集外淋巴样本以尽量减少脑脊液污染。
以非常高的置信度鉴定出50多种明确的蛋白质异构体。iTRAQ报告离子可确定外淋巴和脑脊液之间蛋白质的相对摩尔量。外淋巴中的蛋白质浓度几乎是脑脊液中的三倍。外淋巴中超过三分之一的蛋白质是蛋白酶抑制剂，丝氨酸蛋白酶抑制剂是主要类别。载脂蛋白占16%。15%的蛋白质是酶。白蛋白是最丰富的单一蛋白质（14%）。外淋巴/脑脊液比值相对较高的蛋白质包括广谱蛋白酶抑制剂和载脂蛋白。
在外淋巴中发现的一些蛋白质，如白蛋白和高分子量激肽原，已被证明通过吸附到装置材料上而参与生物污染。相对大量的载脂蛋白和白蛋白可能作为酸性和亲脂性药物的储存库。α-2-糖蛋白可以结合碱性药物。
外淋巴的蛋白质组成与脑脊液相似，但其含量高2.8倍。蛋白酶抑制剂是最大的蛋白质类别。
