Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P R China.
J Proteomics. 2012 Jun 6;75(10):2879-91. doi: 10.1016/j.jprot.2011.12.040. Epub 2012 Jan 10.
Sertoli cell only syndrome (SCOS) is one of the main causes leading to the abnormal spermatogenesis. However, the mechanisms for abnormal spermatogenesis in SCOS are still unclear. Here, we analyzed the clinical testis samples of SCOS patients by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to find the key factors contributing to SCOS. Thirteen differential proteins were identified in clinical testis samples between normal spermatogenesis group and SCOS group. Interestingly, in these differential proteins, Heterogeneous nuclear ribonucleoprotein L(HnRNPL) was suggested as a key regulator involved in apoptosis, death and growth of spermatogenic cells by String and Pubgene bioinformatic programs. Down-regulated HnRNPL in testis samples of SCOS patients was further confirmed by immunohistochemical staining and western blotting. Moreover, in vitro and in vivo experiments demonstrated that knockdown of HnRNPL led to inhibited proliferation, increased apoptosis of spermatogenic cell but decreased apoptosis of sertoli cells. Expression of carcinoembryonic antigen-related cell adhesion molecule 1 in GC-1 cells or expression of inducible nitric oxide synthases in TM4 sertoli cells, was found to be regulated by HnRNPL. Our study first shows HnRNPL as a key factor involved in the spermatogenesis by functional proteomic studies of azoospermia patients with sertoli cell only syndrome. This article is part of a Special Issue entitled: Proteomics: The clinical link.
唯支持细胞综合征(SCOS)是导致生精异常的主要原因之一。然而,SCOS 导致生精异常的机制尚不清楚。在这里,我们通过二维凝胶电泳(2-DE)和基质辅助激光解吸飞行时间质谱(MALDI-TOF/TOF MS)分析了 SCOS 患者的临床睾丸样本,以寻找导致 SCOS 的关键因素。在正常生精组和 SCOS 组的临床睾丸样本中,共鉴定出 13 种差异蛋白。有趣的是,在这些差异蛋白中,STRING 和 Pubgene 生物信息学程序提示异质核核糖核蛋白 L(HnRNPL)是一种参与生精细胞凋亡、死亡和生长的关键调节因子。免疫组织化学染色和 Western blot 进一步证实了 SCOS 患者睾丸样本中 HnRNPL 的下调。此外,体外和体内实验表明,下调 HnRNPL 导致生精细胞增殖抑制、凋亡增加,而支持细胞凋亡减少。GC-1 细胞中癌胚抗原相关细胞黏附分子 1 的表达或 TM4 支持细胞中诱导型一氧化氮合酶的表达,发现受 HnRNPL 调节。我们的研究首次通过对唯支持细胞综合征患者的无精子症功能蛋白质组学研究,将 HnRNPL 作为参与生精的关键因素之一进行了研究。本文是一个题为“蛋白质组学:临床联系”的特刊的一部分。