Suppression of Apoptosis in the Protein Kinase Cδ Null Mouse in Vivo

• DOI: 10.1074/jbc.m507851200
• Publication Date: 2006-02-02T01:58:47Z
• Authors: Michael J. Humphries; Kirsten H. Limesand; Jonathan C. Schne...; Keiichi I. Nakayama; Steven M. Anderson; Mary E. Reyland
• Keywords: Mice, Knockout; 0303 health sciences; JNK Mitogen-Activated Protein Kinases; Apoptosis; Salivary Glands; Adenoviridae; Mitochondria; Mice, Inbred C57BL; Mice; Protein Kinase C-delta; 03 medical and health sciences; Gamma Rays; Transduction, Genetic; Animals; Female; Tumor Suppressor Protein p53; DNA Damage

Protein kinase C (PKC) delta is an essential regulator of mitochondrial dependent apoptosis in epithelial cells. We have used the PKCdelta(-/-) mouse to ask if loss PKCdelta protects salivary glands against gamma-irradiation-induced vivo and explore mechanism underlying protection from apoptosis. show that gamma-irradiation results a robust induction parotid wild type mice, whereas suppressed by greater than 60% mice. Primary cells mice are defective as indicated suppression etoposide-induced cytochrome c release, poly(ADP-ribose) polymerase cleavage, caspase-3 activation. Notably, apoptotic responsiveness can be restored re-introduction adenoviral transduction. Etoposide activation p53 similar primary PKCdelta(+/+) indicating functions downstream DNA damage response. In contrast, c-Jun amino-terminal reduced C5 cells, which express dominant inhibitory mutant PKCdelta. Similarly, gamma-irradiated These studies indicate role for response upstream damage-induced vitro.