Roles of protein kinase C delta in the accumulation of P53 and the induction of apoptosis in H2O2-treated bovine endothelial cells.
To clarify the signaling pathways of oxidative stress-induced apoptosis in bovine aortic endothelial cells (BAEC), we treated cells with 1 mM H2O2 and investigated the roles of protein kinase C delta (PKC delta) and Ca2+ in the accumulation of p53 associated with apoptosis. The treatment of cells with H2O2 caused the accumulation of p53, which was inhibited by rottlerin (a PKC delta inhibitor) but not by BAPTA-AM (an intracellular Ca2+ chelator). PKC delta itself was activated through the phosphorylation at tyrosine residues. H2O2 induced the release of cytochrome c and the activation of caspases 3 and 9, and these apoptotic signals were inhibited by rottlerin and BAPTA-AM. These results suggest that PKC delta contributes to the accumulation of p53 and that Ca2+ plays a role in downstream signals of p53 leading to apoptosis in H2O2-treated BAEC.
Niwa
Koichi
K
Laboratory of Biofluid Dynamics, Research Institute for Electronic Science, Hokkaido University, Sapporo 060-0812, Japan. niwa@bfd.es.hokudai.ac.jp
Inanami
Osamu
O
Yamamori
Tohru
T
Ohta
Toshio
T
Hamasu
Taku
T
Karino
Takeshi
T
Kuwabara
Mikinori
M
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D010766:Phosphorylation; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051745:Protein Kinase C-delta; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000098:Acetophenones; D001578:Benzopyrans; D002614:Chelating Agents; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D016877:Oxidants; D016159:Tumor Suppressor Protein p53; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D014443:Tyrosine; D004533:Egtazic Acid; D006861:Hydrogen Peroxide; C085746:rottlerin; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D002118:Calcium