Cocoa procyanidins protect PC12 cells from hydrogen-peroxide-induced apoptosis by inhibiting activation of p38 MAPK and JNK.
Oxidative stress induced by reactive oxygen species has been strongly associated with the pathogenesis of neurodegenerative disorders, including Alzheimer's disease. In this study, we investigated the possible protective effects of a cocoa procyanidin fraction (CPF) and procyanidin B2 (epicatechin-(4beta-8)-epicatechin) - a major polyphenol in cocoa - against apoptosis of PC12 rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H(2)O(2)). CPF (1 and 5 microg/ml) and procyanidin B2 (1 and 5 microM) reduced PC12 cell death caused by H(2)O(2), as determined by MTT and trypan blue exclusion assays. CPF and procyanidin B2 attenuated the H(2)O(2)-induced fragmentation of nucleus and DNA in PC12 cells. Western blot data demonstrated that H(2)O(2) induced cleavage of poly(ADP-ribose)polymerase (PARP), downregulated Bcl-X(L) and Bcl-2 in PC12 cells. Pretreatment with CPF or procyanidin B2 before H(2)O(2) treatment diminished PARP cleavage and increased Bcl-X(L) and Bcl-2 expression compared with those only treated with H(2)O(2). Activation of caspase-3 by H(2)O(2) was inhibited by pretreatment with CPF or procyanidin B2. Furthermore, H(2)O(2)-induced rapid and significant phosphorylation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and both of these effects were attenuated by CPF or procyanidin B2 treatment. These results suggest that the protective effects of CPF and procyanidin B2 against H(2)O(2)-induced apoptosis involve inhibiting the downregulation of Bcl-X(L) and Bcl-2 expression through blocking the activation of JNK and p38 MAPK.
Cho
Eun Sun
ES
Department of Agricultural Biotechnology, Center for Agricultural Biomaterials, Seoul National University, San 56-1, Shillim-dong, Gwanak-gu, Seoul 151-921, Republic of Korea.
Lee
Ki Won
KW
Lee
Hyong Joo
HJ
D000818:Animals; D017209:Apoptosis; D044946:Biflavonoids / Q000494:pharmacology*; D002099:Cacao / Q000737:chemistry*; D002392:Catechin / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D044946:Biflavonoids; D044945:Proanthocyanidins; C479580:procyanidin B2; D002392:Catechin; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases