title: iTRAQ-based proteomic profiling of human serum reveals down-regulation of platelet basic protein and apolipoprotein B100 in patients with hematotoxicity induced by chronic occupational benzene exposure.
abstract: Benzene is an important industrial chemical and an environmental contaminant, but the pathogenesis of hematotoxicity induced by chronic occupational benzene exposure (HCOBE) remains to be elucidated. To gain an insight into the molecular mechanisms and developmental biomarkers for HCOBE, isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) were utilized. Identification and quantitation of differentially expressed proteins between HCOBE cases and healthy control were thus made. Expressions of selected proteins were confirmed by western blot and further validated by ELISA. A total of 159 unique proteins were identified (≥95% confidence), and relative expression data were obtained for 141 of these in 3 iTRAQ experiments, with fifty proteins found to be in common among 3 iTRAQ experiments. Plasminogen (PLG) was found to be significantly up-regulated, whereas platelet basic protein (PBP) and apolipoprotein B100 (APOB100) were significantly down-regulated in the serum of HCOBE cases. Additionally, the altered proteins were associated with the molecular functions of binding, catalytic activity, enzyme regulator activity and transporter activity, and involved in biological processes of apoptosis, developmental and immune system process, as well as response to stimulus. Furthermore, differential expressions of PLG, PBP and APOB100 were confirmed by western blot, and the clinical relevance of PBP and APOB100 with HCOBE was validated by ELISA. Overall, our results showed that lowered expression of PBP and APOB100 proteins served as potential biomarkers of HCOBE, and may play roles in the benzene-induced immunosuppressive effects and disorders in lipid metabolism.
authors.affiliation: Guangdong Prevention and Treatment Center for Occupational Diseases, 68 Haikang St., Xingang Rd. W., Guangzhou 510300, PR China. zhenliehuang@gmail.com
authors.forename: Zhenlie
authors.initials: Z
authors.lastname: Huang
authors.forename: Hailan
authors.initials: H
authors.lastname: Wang
authors.forename: Hanlin
authors.initials: H
authors.lastname: Huang
authors.forename: Lihua
authors.initials: L
authors.lastname: Xia
authors.forename: Cishan
authors.initials: C
authors.lastname: Chen
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Qiu
authors.forename: Jiabin
authors.initials: J
authors.lastname: Chen
authors.forename: Susheng
authors.initials: S
authors.lastname: Chen
authors.forename: Weihui
authors.initials: W
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Lang
authors.forename: Qianling
authors.initials: Q
authors.lastname: Zheng
authors.forename: Banghua
authors.initials: B
authors.lastname: Wu
authors.forename: Guanchao
authors.initials: G
authors.lastname: Lai
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100 / Q000096:biosynthesis* / Q000235:genetics*; D001554:Benzene / Q000009:adverse effects*; D001772:Blood Cell Count; D015153:Blotting, Western; D002853:Chromatography, Liquid; D002908:Chronic Disease; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D010958:Plasminogen / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000145:classification; D040901:Proteomics / Q000379:methods*; D012997:Solvents / Q000009:adverse effects*; D053719:Tandem Mass Spectrometry; D001620:beta-Thromboglobulin / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D053299:Apolipoprotein B-100; C061615:PPBP protein, human; D011506:Proteins; D012997:Solvents; D001620:beta-Thromboglobulin; D010958:Plasminogen; D001554:Benzene