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Title: CDK5 : new insights into its biological function in human brain microvascular endothelial cells
Author: Pennucci, Roberta
ISNI:       0000 0004 2670 6554
Awarding Body: Manchester Metropolitan University
Current Institution: Manchester Metropolitan University
Date of Award: 2009
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Ischaemic stroke is a leading cause of death and disability worldwide Successful therapies reside in a precise knowledge of brain function and pathology. Towards this end, previous work in the MMU laboratory used cDNA microarrays to examine gene expression in an experimental rat model of ischaemic stroke - permanent MCAO - and for the first time in human brain tissue from ischaemic stroke patients. Novel deregulated genes were identified. This study was intended to confirm the reproducibility of the in vivo data in vitro. The results showed that human foetal (cerebral cortical) neurons (HFN), human brain microvascular endothelial cells (HBMEC) and human astrocytes exposed to oxygen-glucose deprivation (OGD) and reperflision in most cases reproduced the gene expression profiling obtained in vivo. This suggests that HFN, HBMEC and astrocytes are good models to analyse gene deregulation after ischaemia in vitro. Further studies will help to determine the significance of such changes. Among the genes deregulated were prp and cdk5. The expression and localisation of these genes/proteins were explored in detail. Increased expression of PrPc gene and protein was found in HFN after OGD, but the significance of this expression change remains to be elucidated. Increased expression of Cdk5 and its activator p35, as well as nuclear translocation of Cdk5, p35 and p-Cdk5 (SI59) were observed in HFN and HBMEC upon ischaemic stimulation in vitro. Nuclear translocation occurred particularly in propidium iodide-positive cells, thus linking nuclear Cdk5 and p35 to cell damage in both cell types. This suggests a new role for Cdk5 in modulating endothelial cell survival following ischaemia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available