Staurosporine-induced apoptosis of immortalized mouse proximal tubule cells 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 protein kinase C but not of cdc-2 kinase in S3 cells. No change in cell cycle distribution was observed in S3 cells treated with STS. However, treatment of S3 cells with STS resulted in a decrease in the level of bcl-2 mRNA expression in the cells. Overexpression of bcl-2 inhibited the degree of STS-induced apoptosis of S3 cells. In conclusion, STS induces apoptosis of mouse S3 cells via inhibition of various protein kinases including protein kinase C, and the apoptosis is modulated by the bcl-2 expression level.
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
M
M
Takeda
M
M
Kobayashi
T
T
Osaki
I
I
Shirato
H
H
Endou