The Role Of Cdk5Kinase Activation In Retinitis Pigmentosa

Objective To study the roles of Cdk5/P25kinase activation in the development of retinitis pigmentosa.Methods18SPF RCS rats and18RCS-rdy+rats were randomized into17-,25-and35-day groups respectively and6rats for each. The rats were sacrificed at corresponding time points and retinal hemogenete was prepared. Expressions of Cdk5, p35, p25and tau phosphorylation in the retinas were detected by Western blot, and the kinase activity of Cdk5/p25was analyzed by quantitative colorimetric assay. All values were expressed as mean±SD, Data were analyzed by software SPSS17.0.Results1. The expressing level of P35protein in the retinas of17-day-old RCS rats was near that of17-day-old RCS-rdy+rats (t=0.52, P>0.05). In25-and35-day-old RCS rats, the expressing levels of P35protein were2.20+0.48and1.23±0.14, which were higher that those of RCS-rdy+rats(1.43±0.13and0.93±0.10), showing significant difference between them (t=3.78、4.28, P<0.05).2. The expression of P25was undetectable at postnatal17days in RCS rats and RCS-rdy+rats, but it showed significantly higher in RCS rats (0.30±0.003and0.23±0.004) than in RCS-rdy+rats (0.04±0.004and0.07±0.004) at postnatal25days and35days (t=121.81、77.51, P<0.05).3. No significant change was found in the expression of Cdk5in RCS rats and RCS-rdy+rats at different ages (all P>0.05).4. The kinase activity of Cdk5/P25did not show significantly different between RCS and RCS-rdy+rats at postnatal17days (t=0.53, P>0.05), but significantly higher kinase activity of Cdk5/P25was seen in RCS rats (0.00583±0.000527and0.00560±0.00043) than in RCS-rdy+rats (0.00385±0.000288and0.00320±0.000681) at postnatal25days and35days (t=8.07,5.97, P<0.05).5. No expression of tau phosphorylation was detected in RCS rats at postnatal17days, but significantly higher tau phosphorylation level was seen in RCS rats at postnatal25days and35days (1.80±0.22and1.23±0.17), which significant diffences in comparison with RCS-rdy+rats at postnatal25days and35days (1.60±0.20and1.04±0.12)(t=4.71、3.17, P<0.05).Conclusions The Cdk5/P25kinase activity was consistent with the expression level of P25and tau phosphorylation in the RCS rats, suggesting the increased amount of P25could induce an increased enzyme activity of Cdk5and the phosphorylation of Cdk5on its substrates might result in more apoptosis of photoreceptor cells. This study confirmed that Cdk5/p25involved in the apoptosis of retinal cells and prolonged activation of Cdk5/p25may be as a possible downstream mechanism for the development of retinitis pigmentosia.