Zhang Lu, Wang Zhuoran, Chen Yulong, Zhang Chi, Xie Shiping, Cui Yinglin, Wang Zhao
MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing 100084, China.
Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China.
J Proteomics. 2015 Aug 3;126:46-53. doi: 10.1016/j.jprot.2015.05.033. Epub 2015 Jun 1.
The association of gender with the treatment outcome during long-term antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients has been controversial. Here, we performed a comparative proteomic analysis of peripheral blood mononuclear cells (PBMC) by using a label-free shotgun method with nano-LC-MS/MS to investigate the gender differences in responses to long-term ART. This analysis enrolled 30 HIV-infected patients (16 males and 14 females), as well as 20 healthy adults (10 males and 10 females) as control. Quantitative real-time RT-PCR and immunoblotting were used to validate the results of proteomic approach. A total of 53 proteins showing differential expression (± 1.5 fold, p < 0.05) were identified in HIV-infected patients versus healthy adults. Of these proteins, 22 proteins showed identical regulation patterns in both men and women, while 31 proteins were gender-specific (21 men-specific and 10 women-specific proteins). Bioinformatics analysis indicated that long-term ART causes up-regulation of apoptosis, oxidative phosphorylation and mitochondrial dysfunction while down-regulation of oxidative stress and immune system process in men compared to women. These findings point to a concept that gender has a significant influence on the outcomes of ART at protein level and women present a potential favorable immunological pattern and recovery during long-term ART.
在人类免疫缺陷病毒（HIV）感染患者的长期抗逆转录病毒治疗（ART）期间，性别与治疗结果之间的关联一直存在争议。在此，我们采用无标记鸟枪法结合纳升液相色谱-串联质谱（nano-LC-MS/MS）对外周血单核细胞（PBMC）进行了比较蛋白质组学分析，以研究长期ART反应中的性别差异。该分析纳入了30名HIV感染患者（16名男性和14名女性），以及20名健康成年人（10名男性和10名女性）作为对照。采用定量实时逆转录-聚合酶链反应（RT-PCR）和免疫印迹法验证蛋白质组学方法的结果。在HIV感染患者与健康成年人中，共鉴定出53种表达差异（±1.5倍，p<0.05）的蛋白质。在这些蛋白质中，22种蛋白质在男性和女性中表现出相同的调节模式，而31种蛋白质具有性别特异性（21种男性特异性蛋白质和10种女性特异性蛋白质）。生物信息学分析表明，与女性相比，长期ART导致男性细胞凋亡、氧化磷酸化和线粒体功能障碍上调，而氧化应激和免疫系统过程下调。这些发现表明，性别在蛋白质水平上对ART结果有显著影响，并且女性在长期ART期间呈现出潜在的有利免疫模式和恢复情况。
