Increased expression of CDK11p58 and cyclin D3 following spinal cord injury in rats.

Protein kinases are critical signalling molecules for normal cell growth and development. CDK11p58 is a p34cdc2-related protein kinase, and plays an important role in normal cell cycle progression. However its distribution and function in the central nervous system (CNS) lesion remain unclear. In this study, we mainly investigated the protein expression and cellular localization of CDK11 during spinal cord injury (SCI). Western blot analysis revealed that CDK11p58 was not detected in normal spinal cord. It gradually increased, reached a peak at 3 day after SCI, and then decreased. The protein expression of CDK11(p58) was further analyzed by immunohistochemistry. The variable immunostaining patterns of CDK11p58 were visualized at different periods of injury. Double immunofluorescence staining showed that CDK11 was co-expressed with NeuN, CNPase and GFAP. Co-localization of CDK11/active caspase-3 and CDK11/proliferating cell nuclear antigen (PCNA) were detected in some cells. Cyclin D3, which was associated with CDK11p58 and could enhance kinase activity, was detected in the normal and injured spinal cord. The cyclin D3 protein underwent a similar pattern with CDK11p58 during SCI. Double immunofluorescence staining indicated that CDK11 co-expressed with cyclin D3 in neurons and glial cells. Coimmunoprecipitation further showed that CDK11p58 and cyclin D3 interacted with each other in the damaged spinal cord. Thus, it is likely CDK11p58 and cyclin D3 could interact with each other after acute SCI. Another partner of CDK11p58 was beta-1,4-galactosyltransferase 1 (beta-1,4-GT 1). The co-localization of CDK11/beta-1,4-GT 1 in the damaged spinal cord was revealed by immunofluorescence analysis. The cyclin D3-CDK4 complexes were also present by coimmunoprecipitation analysis. Taken together, these data suggested that both CDK11 and cyclin D3 may play important roles in spinal cord pathophysiology.