title: Piceatannol attenuates hydrogen-peroxide- and peroxynitrite-induced apoptosis of PC12 cells by blocking down-regulation of Bcl-XL and activation of JNK.
abstract: There is mounting evidence implicating the accumulation of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease. Recently, considerable attention has been focused on identifying naturally occurring antioxidants that are able to reduce excess ROS and RNS, thereby protecting against oxidative stress and neuron death. The present study investigated the possible protective effects of piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), which is present in grapes and other foods, on hydrogen-peroxide- and peroxynitrite-induced oxidative cell death. PC12 rat pheochromocytoma (PC12) cells treated with hydrogen peroxide or SIN-1 (a peroxynitrite-generating compound) exhibited apoptotic death, as determined by nucleus condensation and cleavage of poly(ADP-ribose)polymerase (PARP). Piceatannol treatment attenuated hydrogen-peroxide- and peroxynitrite-induced cytotoxicity, apoptotic features, PARP cleavage and intracellular ROS and RNS accumulation. Treatment of PC12 cells with hydrogen peroxide or SIN-1 led to down-regulation of Bcl-X(L) and activation of caspase-3 and -8, which were also inhibited by piceatannol treatment. Hydrogen peroxide or SIN-1 treatment induced phosphorylation of the c-Jun-N-terminal kinase (JNK), which was inhibited by piceatannol treatment. Moreover, SP600125 (a JNK inhibitor) significantly inhibited hydrogen-peroxide- and peroxynitrite-induced PC12 cell death, revealing inactivation of the JNK pathway as a possible molecular mechanism for the protective effects of piceatannol against hydrogen-peroxide- and peroxynitrite-induced apoptosis of PC12 cells. Collectively, these findings suggest that the protective effect of piceatannol against hydrogen-peroxide- and peroxynitrite-induced apoptosis of PC12 cells is associated with blocking the activation of JNK and the down-regulation of Bcl-XL.
authors.affiliation: Department of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Mi-Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D013267:Stilbenes / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000873:Anthracenes; C494813:Bcl2l1 protein, rat; D013267:Stilbenes; D051020:bcl-X Protein; D030421:Peroxynitrous Acid; C432165:pyrazolanthrone; C041525:3,3',4,5'-tetrahydroxystilbene; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053181:Caspase 8