Expression of cyclin‐dependent kinase 5 mRNA and protein in the human brain following acute ischemic stroke

• Published in: The FASEB journal 2006-03, Vol.20 (4), p.A460-A460
• Main Authors: Mitsios, Nicholas, Pennucci, Roberta, Krupinski, Jerzy, Sanfeliu, Coral, Gaffney, John, Kumar, Patricia, Kumar, Shant, Slevin, Mark
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A460-d

Cyclin‐dependent kinase 5 (Cdk5) is expressed in neurons, and growing evidence suggests that it can promote neuronal death. Little has been published on Cdk5 expression after stroke in man. In this study, RT‐PCR, western blotting and immunohistochemistry have been employed to study Cdk5 expression in human post‐mortem stroke tissue, and in human neurons, astrocytes and brain endothelial cells exposed to oxygen‐glucose deficiency and reperfusion. Since Cdk5 activation results both from binding to its regulatory subunit p35 and from phosphorylation, expression of both p35 and phosphorylated Cdk5 (p‐Cdk5) was investigated. An increase in the number of neurons, astrocytes and microvessels stained for Cdk5, p‐Cdk5 and p35 occurred in the infarct and penumbra of patients after stroke. Staining became irregular and clumped in the cytoplasm and nuclear translocation occurred. Association of Cdk5 with apoptosis after stroke was found, as Cdk5 colocalized with TUNEL positive neurons and p‐Cdk5 was found in the nucleus of active caspase‐3 stained cells. Similar upregulation in human cerebral cortical foetal neurons, astrocytes and human brain microvascular endothelial cells (HBMEC) subjected to oxygen‐glucose deficiency (OGD) was seen. These results provide evidence for a role of Cdk5 in the events associated with response to ischemic injury. Financial support for this study came from HEFCE and RIHSC.