title: Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals.
abstract: Neurodegenerative disorders such as Alzheimer's disease (AD) are strongly associated with oxidative stress, which is induced by reactive oxygen species (ROS) including hydrogen peroxide (H(2)O(2)). Recent studies suggest that moderate coffee consumption may reduce the risk of neurodegenerative diseases such as AD, but the molecular mechanisms underlying this effect remain to be clarified. In this study, we investigated the protective effects of chlorogenic acid (5-O-caffeoylquinic acid; CGA), a major phenolic phytochemical found in instant decaffeinated coffee (IDC), and IDC against oxidative PC12 neuronal cell death. IDC (1 and 5 microg/ml) or CGA (1 and 5 microM) attenuated H(2)O(2)-induced PC12 cell death. H(2)O(2)-induced nuclear condensation and DNA fragmentation were strongly inhibited by pretreatment with IDC or CGA. Pretreatment with IDC or CGA also inhibited the H(2)O(2)-induced cleavage of poly(ADP-ribose) polymerase (PARP), and downregulation of Bcl-X(L) and caspase-3. The accumulation of intracellular ROS in H(2)O(2)-treated PC12 cells was dose-dependently diminished by IDC or CGA. The activation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) by H(2)O(2) in PC12 cells was also inhibited by IDC or CGA. Collectively, these results indicate that IDC and CGA protect PC12 cells from H(2)O(2)-induced apoptosis by blocking the accumulation of intracellular ROS and the activation of MAPKs.
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Cho
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Mun Kyung
authors.initials: MK
authors.lastname: Hwang
authors.forename: Nam Joo
authors.initials: NJ
authors.lastname: Kang
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002726:Chlorogenic Acid / Q000302:isolation & purification / Q000494:pharmacology; D003069:Coffee / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494813:Bcl2l1 protein, rat; D003069:Coffee; D018696:Neuroprotective Agents; D010636:Phenols; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; D002726:Chlorogenic Acid; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3