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 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.110.176925
4099  - http://jpet.aspetjournals.org/content/early/2011/03/11/jpet.110.176925.short
4100  - http://jpet.aspetjournals.org/content/early/2011/03/11/jpet.110.176925.full
AB  - Kaempferol, a natural flavonoid isolated from various plant sources, has been identified as a potential neuroprotectant. Here, 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 anti-apoptotic protein Bcl-2 and activation of pro-apoptotic caspase-3. Kaempferol inhibited 4-HNE-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). Importantly, kaempferol directly bound p47phox, a cytosolic subunit of NADPH oxidase (NOX), and significantly inhibited 4-HNE-induced activation of NOX. The anti-apoptotic 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 the p47phox of NOX and potently inhibiting activation of NOX-JNK signaling pathway in neuron-like cells. Altogether, these results suggest that kaempferol may be a potent prophylactic against NOX-mediated neurodegeneration.