title: Caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid up-regulate NQO1 expression and prevent H₂O₂-induced apoptosis in primary cortical neurons.
abstract: Neurodegenerative disorders are strongly associated with oxidative stress, which is induced by reactive oxygen species including hydrogen peroxide (H₂O₂). Epidemiological studies have suggested that coffee may be neuroprotective, but the molecular mechanisms underlying this effect have not been clarified. In this study, we investigated the protective effects of caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid (5-O-caffeoylquinic acid), which is present in both caffeinated and decaffeinated coffee, against oxidative neuronal death. H₂O₂-induced apoptotic nuclear condensation in neuronal cells was strongly inhibited by pretreatment with caffeinated coffee, decaffeinated coffee, or chlorogenic acid. Pretreatment with caffeinated coffee, decaffeinated coffee, or chlorogenic acid inhibited the H₂O₂-induced down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-X(L) while blocking H₂O₂-induced pro-apoptotic cleavage of caspase-3 and pro-poly(ADP-ribose) polymerase. We also found that caffeinated coffee, decaffeinated coffee, and chlorogenic acid induced the expression of NADPH:quinine oxidoreductase 1 (NQO1) in neuronal cells, suggesting that these substances protect neurons from H₂O₂-induced apoptosis by up-regulation of this antioxidant enzyme. The neuroprotective efficacy of caffeinated coffee was similar to that of decaffeinated coffee, indicating that active compounds present in both caffeinated and decaffeinated coffee, such as chlorogenic acid, may drive the effects.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Siyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Jaesung
authors.initials: J
authors.lastname: Shim
authors.forename: Hyo Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Jaekyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Hee
authors.initials: H
authors.lastname: Yang
authors.forename: Jiman
authors.initials: J
authors.lastname: Park
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Choi
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Yoon
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002110:Caffeine / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002726:Chlorogenic Acid / Q000494:pharmacology*; D003069:Coffee; D017931:DNA Primers; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone); D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D003069:Coffee; D017931:DNA Primers; D002726:Chlorogenic Acid; D002110:Caffeine; D006861:Hydrogen Peroxide; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse