PT - JOURNAL ARTICLE AU - Young Jin Jang AU - Jiyoung Kim AU - Jaesung Shim AU - Jaekyoon Kim AU - Sanguine Byun AU - Min-Ho Oak AU - Ki Won Lee AU - Hyong Joo Lee TI - Kaempferol Attenuates 4-Hydroxynonenal-Induced Apoptosis in PC12 Cells by Directly Inhibiting NADPH Oxidase AID - 10.1124/jpet.110.176925 DP - 2011 Jun 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 747--754 VI - 337 IP - 3 4099 - http://jpet.aspetjournals.org/content/337/3/747.short 4100 - http://jpet.aspetjournals.org/content/337/3/747.full SO - J Pharmacol Exp Ther2011 Jun 01; 337 AB - 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 p47phox, 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 p47phox 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.