4-Hydroxy-2-nonenal modified histone-H2A: A possible antigenic stimulus for systemic lupus erythematosus autoantibodies

被引：32

作者：

Alzolibani, Abdullateef A. ^{[1
]}

Al Robaee, Ahmad A. ^{[1
]}

Al-Shobaili, Hani A. ^{[1
]}

Rasheed, Zafar ^{[2
]}

机构：

[1] Qassim Univ, Dept Dermatol, Coll Med, Buraydah 51452, Saudi Arabia

[2] Qassim Univ, Coll Med, Dept Med Biochem, Buraydah 51452, Saudi Arabia

来源：

CELLULAR IMMUNOLOGY | 2013年 / 284卷 / 1-2期

关键词：

Histone-H2A; Nucleoprotein; SLE; Autoimmunity; 4-Hydroxy-2-nonenal; HNE-H2A; HUMAN SERUM-ALBUMIN; LIPID-PEROXIDATION PRODUCTS; ELEVATED OXIDATIVE STRESS; TYPE-1; DIABETES-MELLITUS; IMMUNOGLOBULIN-G; POTENTIAL ROLE; DNA-DAMAGE; ANTIBODIES; PROTEIN; AUTOIMMUNITY;

D O I：

10.1016/j.cellimm.2013.07.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Protein modifications by 4-hydroxy-2-nonenals (HNE) are involved in various diseases. Histones are DNA protective nucleoprotein, which adopt different structures under oxidative stress. This study was undertaken to test the role of HNE-modified-histone-H2A (HNE-H2A) in systemic lupus erythematosus (SLE). Our data revealed that HNE-mediated-lipid peroxidation in histone-H2A caused alteration in histidine, lysine and cystein residues. In addition, protein carbonyl contents were also high in HNE-H2A. HNE-specific quencher, L-carnosine further reiterates HNE-modifications. Specificity of autoantibodies from SLE patients (n = 48) were analyzed towards HNE-H2A and their results were compared with sex- and age-matched controls (n = 36). SLE autoantibodies show preferential binding to HNE-H2A in comparison with histone-H2A (p < 0.0001). Furthermore, HNE-H2A was also detected in SLE peripheral blood mononuclear cells. In conclusion, this is the first study to demonstrate the role of HNE-modified-histone in SLE. Preferential binding of HNE-H2A by affinity purified SLE-IgG pointed out the likely role of HNE-H2A in the initiation/progression of SLE. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：154 / 162

页数：9

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