An integrative proteomics metabolomics based strategy reveals the mechanisms involved in wasp sting induced acute kidney injury. (15th January 2022)

• Record Type: Journal Article
• Authors: Yuan, Hai; Gao, Zhao; Chen, Guang; Peng, Changkun; Sun, Yujun; Jiang, Binbin; Zhou, Hongyu; Cheng, Yong; Hu, Fengqi; Zhang, Qi
• Is Part Of: Toxicon. Volume 205(2022)
• Page Start: 1
• Page End: 10
• Publication Date: 2022-01-15
• Subjects: Metabolomics -- Proteomics -- Wasp sting -- Acute kidney injury -- Rhabdomyolysis -- Hemolysis; AKI acute kidney injury -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- CA3 carbonic anhydrase 3 -- CK creatine kinase -- FC fold change -- GO Gene Ontology -- HPLC-ESI-MS/MS ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry -- KDIGO Kidney Disease Improving Global Outcome -- TCEP tris (2-carboxyethyl) phosphine -- CAA chloroacetamide -- SDC sodium deoxycholate -- KEGG Kyoto Encyclopedia of Genes and Genomes -- LDH lactate dehydrogenase -- MYL3 myosin light chain 3 -- NAKI without AKI group -- OPLS-DA orthogonal partial least square discriminant analysis -- PC phosphatidylcholine -- PE phosphatidylethanolamine -- PLA phospholipase A1 -- RBCs red blood cells -- Scr serum creatinine -- SM sphingomyelins; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2021.11.005
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: The pathophysiological mechanisms involved in wasp-sting-induced acute kidney injury (AKI) remain largely unknown. Here, we combined proteomics and metabolomics to investigate the mechanisms behind multiple wasp sting-induced AKI. Interestingly, we found many differentially abundant proteins in the serum of AKI group compared with that of the non-AKI and control groups, involved in several metabolic pathways and the regulation of cellular processes. In addition, we also detected differentially abundant metabolites in the AKI group; among them many were involved in the glycerophospholipid metabolic pathway (the key pathway in the context of AKI): 50 metabolites, all downregulated in the AKI group. Importantly, the convergent analysis of metabolomics and proteomics data revealed that biomarkers of rhabdomyolysis (CA 3, MYL3, and LDH) and hemolysis (ALT and LDH) were integrated into a regulatory network with phospholipid metabolism products in the AKI group, indicating that wasp sting-induced AKI is secondary to rhabdomyolysis and intravascular hemolysis. Of note, such a phenotype suggests the disruption of the membrane of skeletal muscle cells and red blood cells mediated by the phospholipase A1 (PLA1), PLA2, and mastoparan in the wasp venom, via the disruption of membrane glycerophospholipids. Overall, our results highlight a potential new mechanism behind wasp sting-induced AKI and suggest that PLA inhibitors may be potential agents for the treatment of this condition. Highlights: The mechanisms behind wasp-sting-induced acute kidney injury were investigated. The differentially expressed proteins in wasp-sting-induced acute kidney injury patients are involved in metabolic pathways. The glycerophospholipid metabolic pathway is the key pathway associated with wasp-sting-induced acute kidney injury. Phospholipase A1 inhibitors may be promising agents for the treatment of wasp sting-induced acute kidney injury.