The levels of cdk5 and p35 proteins and tau phosphorylation are reduced during neuronal apoptosis

Cyclin-dependent kinase 5 (cdk5) is believed to be involved in the phosphorylation of tau protein. We studied the expression of the protein levels of cdk5 and the neuron-specific cdk5 activator p35 as well as cdk5 activity and tau phosphorylation during apoptosis in rat hippocampal neuronal cultures. We observed that in cells treated with etoposide, cyclosporin A, 4-hydroxynonenal (HNE), or okadaic acid, there was an early reduction in the protein levels of p35, and later also in cdk5 with all treatments except etoposide. The level of p25, a calpain cleavage product of p35 suggested to have increased ability to activate cdk5, was reduced paralleling the amount of p35. The changes in the p35 and p25 protein levels coincided with decreases in cdk5 activity and tau phosphorylation after treatment with HNE and etoposide. However, the relationship between the p35 and p25 levels and cdk5 activity was complex. We conclude that neuronal apoptosis is accompanied with a decrease in the levels of p35, p25, and cdk5, and tau phosphorylation. These changes may reinforce the neuronal damage.