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Novel apoptotic mechanism of bioactive flavonoids in obesity
Author(s) -
Sergeev Igor N
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.224.6
Subject(s) - apoptosis , genistein , microbiology and biotechnology , signal transduction , calpain , isoflavones , intracellular , programmed cell death , chemistry , caspase , biology , biochemistry , endocrinology , enzyme
Modulating apoptosis is emerging as a promising strategy for prevention and treatment of obesity. Effects of flavonoids on the cell‐death fate are mediated via multiple signaling pathways converging on cellular Ca 2+ (Sergeev, 2009). Ca 2+ signaling has been implicated in regulation of apoptosis, however, the flavonoid‐activated Ca 2+ ‐dependent apoptotic molecular targets have not been identified. We investigated mechanism of flavonoid‐induced apoptosis in obesity using a model of mature mouse 3T3‐L1 adipocytes. The results obtained demonstrated that soy isoflavones (genistein) and polymethoxyflavones from orange peel induce the apoptotic Ca 2+ signal, sustained increase in concentration of intracellular Ca 2+ , in adipocytes in a concentration‐ and time‐dependent fashion. The flavonoid‐induced Ca 2+ increase was associated with activation of Ca 2+ ‐dependent μ‐calpain and Ca 2+ /calpain‐dependent caspase‐12. The activation of these proteases appears to be sufficient for executing morphological and biochemical consequences attributed to apoptosis. These findings indicate that flavonoids can trigger the apoptosis‐initiating Ca 2+ signal and recruit Ca 2+ ‐dependent apoptosis‐executing effectors. Targeting of Ca 2+ signaling in mature adipocytes via dietary supplementation with flavonoids capable of inducing apoptotic cell death can represent an effective, safe and affordable preventive and therapeutic approach to obesity. Supported by USDA 2009‐35200‐05008, SD00H325, and WellGen.