title: EOP, a newly synthesized ethyl pyruvate derivative, attenuates the production of inflammatory mediators via p38, ERK and NF-κB pathways in lipopolysaccharide-activated BV-2 microglial cells.
abstract: Microglia-induced neuroinflammation is an important pathological mechanism influencing various neurodegenerative disorders. Excess activation of microglia produces a myriad of proinflammatory mediators that decimate neurons. Hence, therapeutic strategies aimed to suppress the activation of microglia might lead to advancements in the treatment of neurodegenerative diseases. In this study, we synthesized a novel ethyl pyruvate derivative, named EOP (S-ethyl 2-oxopropanethioate) and studied its effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in rat primary microglia and mouse BV-2 microglia. EOP significantly decreased the production of NO, inducible nitric oxide synthase, cyclooxygenase and other proinflammatory cytokines, such as interleukin (IL)-6, IL-1β and tumor necrosis factor-α, in LPS-stimulated BV-2 microglia. The phosphorylation levels of extracellular regulated kinase, p38 mitogen-activated protein kinase, and nuclear translocation of NF-κB were also inhibited by EOP in LPS-activated BV-2 microglial cells. Overall, our observations indicate that EOP might be a promising therapeutic agent to diminish the development of neurodegenerative diseases associated with microglia activation.
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
authors.forename: Soon
authors.initials: S
authors.lastname: Min
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
authors.forename: Sandeep Vasant
authors.initials: SV
authors.lastname: More
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Branch of Immune and Cell Therapy, National Cancer Center, Goyang 410-769, Korea.
authors.forename: Sae-Bom
authors.initials: SB
authors.lastname: Jeon
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Branch of Immune and Cell Therapy, National Cancer Center, Goyang 410-769, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea. choidk@kku.ac.kr.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D011773:Pyruvates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D011773:Pyruvates; C000599695:S-ethyl 2-oxopropanethioate; C046522:ethyl pyruvate; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases