title: Label-free proteomic analysis of PBMCs reveals gender differences in response to long-term antiretroviral therapy of HIV.
abstract: 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.
authors.affiliation: MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Zhuoran
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Xie
authors.affiliation: Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Cui
authors.affiliation: MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: zwang@tsinghua.edu.cn.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics; D012727:Sex Characteristics
chemical_list: D044966:Anti-Retroviral Agents; D020543:Proteome
keywords: Antiretroviral therapy; Gender; HIV; Label-free; Proteomic