Protein kinase C involvement in deoxycholate-induced apoptosis in human gastric cells.
Bile acids, such as deoxycholic acid (DC), are known to mediate some of their actions by differentially activating various protein kinase C (PKC) isoforms. This study confirms that DC induces apoptosis in gastric epithelial cells through PARP and caspase cascade activation, and examined the role of PKC in DC-induced apoptosis. We found increased activation of PKC in membrane fractions in response to DC that was concentration and time related. The PKC (beta(I)) isoform expression increased with translocation into the cell membrane fraction after DC (300 microM) stimulation. In contrast, PKCepsilon expression markedly decreased in response to DC treatment in a time- and concentration-dependent manner. In addition, this process was regulated by caspases, since the pan-caspase inhibitor z-VAD-fmk and caspase-3-, -6-, and -9-specific inhibitors prevented PKC (beta(I)) and (epsilon epsilon processing induced by DC. Treatment with the caspase-8-specific inhibitor, however, did not affect expression of either PKC isoform. No significant differences in the apoptotic response were observed when PKC (epsilon) overexpressed cells were exposed to DC in the presence of calcium-dependent conventional PKC inhibitors (Gö 6850 or Gö 6976). Our findings demonstrate that PKC is activated in gastric epithelial cells treated with DC with the PKC (beta(I)) and PKC (epsilon) isoforms being particularly involved in this process. The processing of PKC (beta(I) and epsilon) was shown to be closely regulated by caspases; however, modulations in PKC isoform concentrations by themselves have no effect on the apoptotic death of gastric mucosal cells induced by DC.
Redlak
Maria J
MJ
Department of Surgery, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia 23298-0568, USA.
Power
Jacinda J
JJ
Miller
Thomas A
TA
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004847:Epithelial Cells / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology / Q000502:physiology; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D020033:Protein Isoforms; D003840:Deoxycholic Acid; D011065:Poly(ADP-ribose) Polymerases; D011493:Protein Kinase C; D020169:Caspases