Proteomic analysis of hippocampal proteins in acrylamide-exposed Wistar rats
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Acrylamide has been used industrially and also found in certain foods cooked at high temperatures. Previous reports described acrylamide-related human intoxication who presented with ataxia, memory impairment, and/or illusion. The aim of this study was to characterize the molecular mechanisms of neurotoxicity of acrylamide by analyzing the expression levels of various proteins in the hippocampus of rats exposed to acrylamide. Male Wistar rats were administered acrylamide by gavage at 0, 2, and 20 mg/kg for 1 week or 0, 0.2, 2, and 20 mg/kg for 5 weeks. At the end of the experiment, the hippocampus was dissected out and proteins were extracted for two-dimensional difference gel electrophoresis combined with matrix-assisted laser-desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF/MS). MALDI-TOF/TOF/MS identified significant changes in two proteins in the 1-week and 22 proteins in the 5-week exposure groups. These changes were up-regulation in 9 and down-regulation in 13 proteins in the hippocampus of rats exposed to acrylamide at 20 mg/kg for 5 weeks. PANTHER overrepresentation test based on the GO of biological process showed significant overrepresentation in proteins annotated to nicotinamide nucleotide metabolic process, coenzyme biosynthetic process, pyruvate metabolic process, and carbohydrate metabolic process. The test also showed significant overrepresentation in proteins annotated to creatinine kinase activity for the GO of molecular function as well as myelin sheath, cytoplasmic part, and cell body for the GO of cellular component. Comparison with a previous proteomic study on hippocampal proteins in rats exposed to 1-bromopropane identified triosephosphate isomerase, mitochondrial creatine kinase U-type, creatine kinase β-type and proteasome subunit α type-1 as proteins affected by exposure to acrylamide and 1-bromopropane, suggesting a common mechanism of neurotoxicity for soft electrophiles.
KeywordsAcrylamide Proteomic analysis Neurotoxicology Triosephosphate isomerase Soft electrophiles
This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science 26293148, 16H02965, 17H06396, and 17H07105. The authors thank Ms. Yoshiko Murakata for the generous help in proteomic analysis, Dr. Xiao Zhang for help in molecular analysis, and Ms. Yurina Wakayama, Mr. Kyo Morita, Ms. Hana Katano, and Ms. Mami Sakai for their generous help in the experiment. We thank Ms. Satoko Arai for the excellent secretarial support. We also acknowledge the help and support of Dr. Toshio Nakadate throughout the study.
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Conflict of interest
The authors declare no conflict of interest.
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