Wybrane publikacje

The mechanisms regulating cyclin-dependent kinase 5 in hippocampus during systemic inflammatory response: The effect on inflammatory gene expression.

Czapski GA1, Gąssowska M2, Wilkaniec A2, Chalimoniuk M2, Strosznajder JB2, Adamczyk A2.

The mechanisms regulating cyclin-dependent kinase 5 in hippocampus during systemic inflammatory response: The effect on inflammatory gene expression.

1Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: Ten adres pocztowy jest chroniony przed spamowaniem. Aby go zobaczyć, konieczne jest włączenie w przeglądarce obsługi JavaScript..

2Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, ul. Pawińskiego 5, 02-106 Warsaw, Poland.

Neurochem Int. 2016 Feb;93:103-12. doi: 10.1016/j.neuint.2016.01.005. Epub 2016 Jan 21.

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.

Copyright © 2016 Elsevier Ltd. All rights reserved.

KEYWORDS: Cyclin-dependent kinase 5; Hippocampus; Lipopolysaccharide; Neuroinflammation; Systemic inflammation