STAUROSPORINE-INDUCED APOPTOSIS OF IMMORTALIZED MOUSE PROXIMAL TUBULECELLS IS MODULATED BY BCL-2 EXPRESSION LEVEL

Mouse terminal proximal tubule (S3) cells treated with staurosporine ( STS) underwent morphological and biochemical changes characteristic of apoptosis. Treatment of S3 cells with STS, H-7, PMA, herbimycin A or genistein caused DNA fragmentation. STS inhibited the activity of prot ein kinase C but not of cdc-2 kinase in S3 cells. No change in cell cy cle distribution was observed in S3 cells treated with STS. However, t reatment of S3 cells with STS resulted in a decrease in the level of b cl-2 mRNA expression in the cells. Overexpression of bcl-2 inhibited t he degree of STS-induced apoptosis of S3 cells. In conclusion, STS ind uces apoptosis of mouse S3 cells via inhibition of various protein kin ases including protein kinase C, and the apoptosis is modulated by the bcl-2 expression level.