title: The mechanisms regulating cyclin-dependent kinase 5 in hippocampus during systemic inflammatory response: The effect on inflammatory gene expression.
abstract: Cyclin-dependent kinase 5 (Cdk5) is critical for nervous system's development and function, and its aberrant activation contributes to pathomechanism of Alzheimer's disease and other neurodegenerative disorders. It was recently suggested that Cdk5 may participate in regulation of inflammatory signalling. The aim of this study was to analyse the mechanisms involved in regulating Cdk5 activity in the brain during systemic inflammatory response (SIR) as well as the involvement of Cdk5 in controlling the expression of inflammatory genes. Genetic and biochemical alterations in hippocampus were analysed 3 and 12 h after intraperitoneal injection of lipopolysaccharide. We observed an increase in both Cdk5 gene expression and protein level. Moreover, phosphorylation of Cdk5 on Ser159 was significantly enhanced. Also transcription of Cdk5-regulatory protein (p35/Cdk5r1) was augmented, and the level of p25, calpain-dependent cleavage product of p35, was increased. All these results demonstrated rapid activation of Cdk5 in the brain during SIR. Hyperactivity of Cdk5 contributed to enhanced phosphorylation of tau and glycogen synthase kinase 3β. Inhibition of Cdk5 with Roscovitine reduced activation of NF-κB and expression of inflammation-related genes, demonstrating the critical role of Cdk5 in regulation of gene transcription during SIR.
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: gczapski@imdik.pan.pl.
authors.forename: Grzegorz A
authors.initials: GA
authors.lastname: Czapski
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gąssowska
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wilkaniec
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Chalimoniuk
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland.
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Strosznajder
authors.affiliation: Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Adamczyk
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018746:Systemic Inflammatory Response Syndrome / Q000201:enzymology* / Q000235:genetics
chemical_list: D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse
keywords: Cyclin-dependent kinase 5; Hippocampus; Lipopolysaccharide; Neuroinflammation; Systemic inflammation