Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages
Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages
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DOI：
10.1136/ard.2003.012211
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发表时间：
2004-04-01
影响因子：
27.4
通讯作者：
van Venrooij, WJ
中科院分区：
文献类型：
--
作者：
Vossenaar, ER;Radstake, TRD;van Venrooij, WJ
背景：针对含有非标准氨基酸瓜氨酸的蛋白质的抗体对类风湿性关节炎（RA）具有极高的特异性。肽基瓜氨酸可通过精氨酸残基的翻译后转化产生。目的：研究类风湿关节炎（RA）患者外周血和滑液细胞中4种肽基精氨酸脱亚胺酶（PAD）亚型的表达和活性。结果：数据显示，PAD酶对蛋白质的瓜氨酸化是一个在3个水平调节的过程：转录-在外周血中，PAD 2和PAD 4 mRNA主要在单核细胞中表达; PAD 4 mRNA在巨噬细胞中检测不到，PAD 2 mRNA的翻译-翻译受到其39个UTR的分化阶段特异性调节，和活化-PAD蛋白质仅在足够的Ca 2+可用时被活化。如此高的Ca 2+浓度通常不存在于活细胞中。在巨噬细胞中，这是丰富的炎症RA滑膜，波形蛋白是特异性瓜氨酸化后Ca 2 + inflation.Conclusion：PAD 2和PAD 4是最有可能的候选PAD同种型的瓜氨酸化的滑膜蛋白在RA。我们的研究结果表明，瓜氨酸波形蛋白是一个候选的自身抗原在RA。
Background: Antibodies directed to proteins containing the non-standard amino acid citrulline, are extremely specific for rheumatoid arthritis (RA). Peptidylcitrulline can be generated by post-translational conversion of arginine residues. This process, citrullination, is catalysed by a group of calcium dependent peptidylarginine deiminase ( PAD) enzymes.Objective: To investigate the expression and activity of four isotypes of PAD in peripheral blood and synovial fluid cells of patients with RA.Results: The data presented here show that citrullination of proteins by PAD enzymes is a process regulated at three levels: transcription - in peripheral blood PAD2 and PAD4 mRNAs are expressed predominantly in monocytes; PAD4 mRNA is not detectable in macrophages, translation - translation of PAD2 mRNA is subject to differentiation stage-specific regulation by its 39 UTR, and activation - the PAD proteins are only activated when sufficient Ca2+ is available. Such high Ca2+ concentrations are normally not present in living cells. In macrophages, which are abundant in the inflamed RA synovium, vimentin is specifically citrullinated after Ca2+ influx.Conclusion: PAD2 and PAD4 are the most likely candidate PAD isotypes for the citrullination of synovial proteins in RA. Our results indicate that citrullinated vimentin is a candidate autoantigen in RA.