Proteomics analysis of lysine crotonylation and 2-hydroxyisobutyrylation reveals significant features of systemic lupus erythematosus

Abstract

Introduction/objectives To seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis. Method Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls. Results Seventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration. Conclusion Kcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably. Key Points• Antigen processing and presentation and leukocyte transendothelial migration may play key roles in the pathogenesis of SLE.

Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use

“…The genes annotated to these five cannabis use-associated CpGs are relevant to a range of health outcomes. [34][35][36][37][38][39][40][41][42][43][44] The five epigenome-wide significant CpGs are annotated to the nearest genes: LINC01132, ADGRF1, ADAM12, ACTN1, and APOBR. Of these, cg01101459-LINC01132, cg00813162-ACTN1, and cg14237301-APOBR were inversely associated with cannabis use, meaning that individuals who had used cannabis had lower DNAm at these CpG sites compared to those who had never used cannabis.…”

“…35 Genetic variants and differential expression of the ACTN1 have been reported in various diseases, including congenital macrothrombocytopenia, Angelman syndrome, Bowen disease, postmenopausal osteoporosis, lupus erythematosus, and COVID-19. [35][36][37][38]47,48 APOBR (Apolipoprotein B receptor) encodes a receptor protein that binds to dietary triglyceride-rich lipoproteins.…”

Qualitative Proteome-wide Lysine Crotonylation Profiling Reveals Protein Modification Alteration in the Leukocyte Extravasation Pathway in Systemic Lupus Erythematosus

“…Figure E shows the demographic differences between SLE individuals and healthy subjects. From earlier investigations conducted by our lab team, a more comprehensive list of the study population is available . Every participant signed informed consent before being included in the study.…”

Proteomic analysis of protein lysine 2-hydroxyisobutyrylation (Khib) in soybean leaves

“…However, recent studies have shown that this modification also occurs in nonhistone proteins in various compartments of cells. To date, K hib modification has been identified in human or animal [9][10][11][12][13], fungus (Aspergillus flavus [14], Fusarium graminearum [15], Candida albicans [16], bacteria (Proteus mirabilis [17] and Toxoplasma gondii [18]) and plants. All these studies indicate that K hib modification is not only widely present in various organisms, but also involved in a wide variety of physiological functions.…”