COP9 signalosome/Ischemic stroke
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In the context of studying the role of the COP9 signalosome (CSN) in neuroinflammation and ischemic neuronal damage, we studied the effect of the cullin NEDDylation state-modifying drugs MLN4924 and CSN5i-3 in BV2 microglial cells, an immortalized murine cell line featuring many of the characteristics of primary microglia. Owing to its potent inhibitory effect on the NEDDylation cascade, MLN4924 exhibits a CSN5-like anti-inflammatory activity. Csn5i-3 is a small molecule inhibitor that specifically binds to CSN5, while it resides in the CSN holocomplex and blocks its deNEDDylase activity, thus leading to an accumulation of NEDDylated cullins. We performed untargeted mass spectrometry-based proteomics of the cell lysates after treating BV2 cells with these drugs under basal culture stress conditions. The proteomic analysis revealed that MLN4924 and CSN5i-3 substantially altered the microglial proteome. Read less
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Created: 9th Jul 2024 at 13:02
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Projects: SyNergy - published datasets
Institutions: DZNE
Projects: SyNergy - published datasets
Institutions: Klinikum der Universität München
Projects: SyNergy - published datasets
Institutions: Klinikum der Universität München
Public web page: Not specified
Submitter: Rainer Malik
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Assays: Affinity purification coupled with mass spectrometry proteomics, Affinity purification coupled with mass spectrometry proteomics, Affinity purification coupled with mass spectrometry proteomics, Affinity purification coupled with mass spectrometry proteomics, Affinity purification coupled with mass spectrometry proteomics, Affinity purification coupled with mass spectrometry proteomics, Affinity purification coupled with mass spectrometry proteomics, Bottom-up proteomics, Gel-based experiment, Proteomics analysis of brain endothelial cells, Proteomics of Inflammasome, SWATH MS, Shotgun Proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics, Shotgun proteomics
BV2 cells were cultured in full medium in 10 cm cell culture dishes until they were confluent. MLN4924 (500 nM), CSN5i-3 (1 μM), or solvent control (0.01% DMSO) were added and the culturing continued for 6 h. After the incubation, cells were washed once with PBS, removed from the cell culture plate with a scraper, collected in tubes, and centrifuged in 1.5 ml Eppendorf tubes for 3 min to remove remaining PBS buffer, snap-frozen, and stored at -80 °C until further processing. Thereafter cells were ...
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
In the context of studying the role of the COP9 signalosome (CSN) in neuroinflammation and ischemic neuronal damage, we studied the effect of the cullin NEDDylation state-modifying drugs MLN4924 and CSN5i-3 in BV2 microglial cells, an immortalized murine cell line featuring many of the characteristics of primary microglia. Owing to its potent inhibitory effect on the NEDDylation cascade, MLN4924 exhibits a CSN5-like anti-inflammatory activity. Csn5i-3 is a small molecule inhibitor that specifically ...
Creators: Rainer Malik, Christian Behrends, Jürgen Bernhagen
Submitter: Rainer Malik
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