Subacute sarin exposure disrupted the homeostasis of purine and pyrimidine metabolism in guinea pig striatum studied by integrated metabolomic, lipidomic and proteomic analysis. (15th August 2022)

• Record Type: Journal Article
• Authors: Shi, Meng; Zhang, Ruihua; Jin, Qian; Cui, Yalan; Shi, Jingjing; Chen, Xuejun; Shi, Tong; Zhang, Yi; Zhu, Siqing; Zong, Xingxing; Xu, Jianfu; Wang, Chen; Li, Liqin
• Is Part Of: Toxicology letters. Volume 367(2022)
• Page Start: 48
• Page End: 58
• Publication Date: 2022-08-15
• Subjects: ADCY1 adenylate cyclase 1 -- ADCY9 adenylate cyclase 9 -- ADK adenosine kinase -- ADSS adenylosuccinate synthetase isozyme 1 -- AICAMP 5-phosphoribosyl-5-amino-4-imidazole-carboxamide -- AK1 adenylate kinase isoenzyme 1 -- AMP adenosine monophosphate -- AMPD AMP deaminase -- APRT adenine phosphoribosyltransferase -- ATGL adipose triacylglyceride lipase -- BisMePA bismethyl phosphatidic acid -- CDP cytidine diphosphate -- CDP-DAG cytidine diphosphate diacylglycerol -- CDS cytidine diphosphate diacylglycerol synthase -- Cer ceramide -- CEPT choline/ethanolamine phosphotransferase -- CL cardiolipin -- CLS cardiolipin synthase -- CMP cytidylic acid -- CMPK2 cytidine/uridine monophosphate kinase 2 -- CTP cytidine triphosphate -- DAG diacylglycerol -- DHODH dihydroorotate dehydrogenase -- DGK diacylglycerol kinase -- EPT ethanolamine phosphotransferase -- FA fatty acid -- Gln glutamine -- Glu glutamate -- GLS glutaminase -- GM ganglioside -- GMP guanosine monophosphate -- GMK guanylate kinase -- GPS carbamoyl phosphate synthetase -- HexCer hexosylceramide -- HGPRT hypoxanthine-guanine phosphoribosyltransferase -- IMP inosine monophosphate -- ITPA inosine triphosphate pyrophosphatase -- LdMePE lysodimethylphosphatidylethanolamine -- LPC lysophosphatidylcholine -- LPE lysophosphatidylethanolamine -- LPG lysophosphatidylglycerol -- LPLAT lysophosphatidylethanolamine acyl transferase -- MePC methyl phosphatidylcholine -- MGDG monogalactosyldiacylglycerol -- OAHFA O-acyl-omega-hydroxy fatty acids -- OMP orotidine monophosphate -- PA phosphatidic acid -- PC phosphatidylcholine -- PCCT phosphate cytidylyltransferase -- PE phosphatidylethanolamine -- PEMT phosphatidylethanolamine methyltransferase -- PG phosphatidylglycerol -- PGM1 Phosphoglucomutase 1 -- PGS1 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase -- PI phosphatidylinositol -- PLPP3 acidPPc domain-containing protein -- PNP purine nucleoside phosphorylase -- SM sphingomyelin -- ST sulfatide -- S1P sphingosine-1-phosphate -- TG riglyceride -- UDP uridine diphosphate -- UMP uridine monophosphate -- UMPs OMP decarboxylase -- XMP xanthosine monophosphate -- XO xanthine oxidase; Nerve agent -- Neurotoxicity -- Omics -- Sarin -- Striatum; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2022.07.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Abstract: Sarin was used as a chemical weapon due to its high neurotoxicity and mortality. Subacute sarin induced cognitive and behavioral disorder. However, the underlying mechanism is still unclear. Here we offered a multi-omic approach for the analysis of altered metabolites, lipids, and proteins to explore the neurotoxicity of subacute sarin. Guinea pigs were administered between the shoulder blades 16.8 μg/kg of sarin in a volume of 1.0 ml/kg body weight by subcutaneous injection once daily for 14 days. At the end of the final injection, guinea pigs were sacrificed, and striatum were dissected for analysis. A total of 138 different metabolites were identified in the metabolome analysis. Lipids and lipid-like molecules is the largest group (38.41%). For lipidomic analysis, a total of 216 lipids were identified. In proteomic study, over 4300 proteins were identified and quantified. By integrating these enriched components, we demonstrated that the joint pathways disturbed by subacute sarin mainly involving lipid, purine and pyrimidine metabolism in guinea pig striatum. Overall, this study highlights the powerfulness of omics platforms to deepen the understanding of nerve agents caused neurotoxicity. Graphical Abstract: ga1 Highlights: Subacute sarin disturbed the cognitive and motor abilities in guinea pigs. Subacute sarin disturbed purine and pyrimidine metabolism in striatum. Nucleotides play important roles in alleviating neurotoxicity of nerve agents. Omics platforms are useful to deepen the understanding of nerve agents caused neurotoxicity.