Kaempferol attenuates 4-hydroxynonenal-induced apoptosis in PC12 cells by directly inhibiting NADPH oxidase

Young Jin Jang, Jiyoung Kim, Jaesung Shim, Jaekyoon Kim, Sanguine Byun, Min Ho Oak, Ki Won Lee, Hyong Joo Lee

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)747-754
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume337
Issue number3
DOIs
Publication statusPublished - 2011 Jun

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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