ER stress-induced caspase-12 activation is inhibited by PKC in neuronal cells.
Caspase-12 is activated when the cells are exposed to excess levels of various stimuli, which cause endoplasmic reticulum (ER) stress. Protein kinase C (PKC) plays an important role in many signaling pathways in cells, and the activation of PKC has multiple actions in the signaling function of the ER. This study examined whether or not phorbol 12, 13-dibutyrate (PDBu)-induced PKC activation modulates caspase-12 cleavage and it's processing, using a wild type caspase-12 overexpressing neuronal cell line, known as Cas-12 cells. The thapsigargin treatment induced caspase-12 fragmentation in the Cas-12 cells. This was inhibited by PKC, which had previously been stimulated by PDBu. The PDBu treatment attenuated the ER stress-induced translocation of caspase-12 from the ER to the cytoplasm. The caspase-3 specific inhibitor blocked caspase-12 fragmentation, and purified caspase-12 was cleaved by the active caspase-3 in vitro, suggesting that caspase-12 might be a substrate for caspase-3. In addition, the PDBu treatment influenced the decrease of active caspase-3 fragment. These results suggest that an ER stress induces the activation of caspase-12 via caspase-3, and that PKC regulates both caspase-12 and caspase-3 activations in Cas-12 cells.
Lee
W
W
Biomedical Research Center, The Functional Proteomics Center, Korea.
Kim
D H
DH
Boo
J H
JH
Kim
Y H
YH
Park
I-S
IS
Mook-Jung
I
I
D000818:Animals; D015153:Blotting, Western; D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004789:Enzyme Activation; D007150:Immunohistochemistry; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D011994:Recombinant Proteins; D015240:Phorbol 12,13-Dibutyrate; D019284:Thapsigargin; D011493:Protein Kinase C; C506443:Casp12 protein, rat; C505410:Casp3 protein, rat; D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases; C112920:caspase 13