title: Kaempferol attenuates 4-hydroxynonenal-induced apoptosis in PC12 cells by directly inhibiting NADPH oxidase.
abstract: Kaempferol, a natural flavonoid isolated from various plant sources, has been identified as a potential neuroprotectant. In this study, we investigated the protective effect of kaempferol against 4-hydroxynonenal (HNE)-induced apoptosis in PC12 rat pheochromocytoma cells. Kaempferol inhibited 4-HNE-mediated apoptosis, characterized by nuclear condensation, down-regulation of antiapoptotic protein Bcl-2, and activation of proapoptotic caspase-3. Kaempferol inhibited 4-HNE-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). More importantly, kaempferol directly bound p47(phox), a cytosolic subunit of NADPH oxidase (NOX), and significantly inhibited 4-HNE-induced activation of NOX. The antiapoptotic effects of kaempferol were replicated by the NOX inhibitor apocynin, suggesting that NOX is an important enzyme in its effects. Our results suggest that kaempferol attenuates 4-HNE-induced activation of JNK and apoptosis by binding p47(phox) of NOX and potently inhibiting activation of the NOX-JNK signaling pathway in neuron-like cells. Altogether, these results suggest that kaempferol may be a potent prophylactic against NOX-mediated neurodegeneration.
authors.affiliation: World Class University Biomodulation Program, Department of Agricultural Biotechnology, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Jaesung
authors.initials: J
authors.lastname: Shim
authors.forename: Jaekyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Sanguine
authors.initials: S
authors.lastname: Byun
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Oak
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D044949:Kaempferols / Q000819:agonists / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D018696:Neuroprotective Agents / Q000032:analysis / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D014343:Trypan Blue / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000447:Aldehydes; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007211:Indoles; D044949:Kaempferols; D018696:Neuroprotective Agents; C007293:DAPI; C006552:kaempferol; C056165:acetovanillone; D019255:NADPH Oxidases; D048031:JNK Mitogen-Activated Protein Kinases; D014343:Trypan Blue; C027576:4-hydroxy-2-nonenal