Caspase-Mediated Truncation of Tau Potentiates Aggregation
Figure 1
Pharmacological manipulation of caspase activity. (a) presents immunoblots of lysates from cells treated with Z-VAD-fmk, staurosporine, or both, along with untreated controls, probed with antibodies directed against cleaved caspase-3, PARP, tau, and tubulin (as a loading control) as indicated. The accompanying graphs (b) present the mean intensity ratio (±SEM) normalized to untreated controls from 3 immunoblots. Note increased levels activated caspase-3 and PARP cleavage, and reduced levels of tau following staurosporine treatment. Note that Z-VAD-FMK did not reduce steady-state levels of cleaved caspase-3, cleaved PARP, or tau but increased intact PARP (21%), suggesting the presence of ongoing caspase activity and PARP cleavage in these cells prior to treatment. Co-treatment with Z-VDA-fmk attenuated staurosporine-induced caspase activity, PARP, and tau cleavage. The percentage changes were quantified by densitometric analyses of immunoblots. An asterisk indicates statistical significance when compared to untreated controls (, Student’s t-test). (c) presents representative images of DAPI-stained cells. Note presence of healthy, nonapoptotic nuclei, indicating that incubation with staurosporine for 4 hours did not induce apoptosis.
