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
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 microgli...
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MDPI AG
2014-11-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/12/19361 |
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| author | Soon Min Sandeep Vasant More Ju-Young Park Sae-Bom Jeon Shin Young Park Eun-Jung Park Sung-Hwa Yoon Dong-Kug Choi |
| author_facet | Soon Min Sandeep Vasant More Ju-Young Park Sae-Bom Jeon Shin Young Park Eun-Jung Park Sung-Hwa Yoon Dong-Kug Choi |
| author_sort | Soon Min |
| collection | DOAJ |
| description | 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. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T10:57:33Z |
| publishDate | 2014-11-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9914fee86ce4421da4d225ad161856992022-12-21T23:49:26ZengMDPI AGMolecules1420-30492014-11-011912193611937510.3390/molecules191219361molecules191219361EOP, 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 CellsSoon Min0Sandeep Vasant More1Ju-Young Park2Sae-Bom Jeon3Shin Young Park4Eun-Jung Park5Sung-Hwa Yoon6Dong-Kug Choi7Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, KoreaDepartment of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 443-749, KoreaBranch of Immune and Cell Therapy, National Cancer Center, Goyang 410-769, KoreaDepartment of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, KoreaBranch of Immune and Cell Therapy, National Cancer Center, Goyang 410-769, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 443-749, KoreaDepartment of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, KoreaMicroglia-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.http://www.mdpi.com/1420-3049/19/12/19361ethyl pyruvate derivativelipopolysaccharidemicroglianeuroinflammationneurodegenerative diseasesprimary microglia |
| spellingShingle | Soon Min Sandeep Vasant More Ju-Young Park Sae-Bom Jeon Shin Young Park Eun-Jung Park Sung-Hwa Yoon Dong-Kug Choi 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 Molecules ethyl pyruvate derivative lipopolysaccharide microglia neuroinflammation neurodegenerative diseases primary microglia |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | ethyl pyruvate derivative lipopolysaccharide microglia neuroinflammation neurodegenerative diseases primary microglia |
| url | http://www.mdpi.com/1420-3049/19/12/19361 |
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