Polymethoxyflavones activate Ca2+-dependent apoptotic targets in adipocytes.
Identifieur interne : 001D33 ( Main/Curation ); précédent : 001D32; suivant : 001D34Polymethoxyflavones activate Ca2+-dependent apoptotic targets in adipocytes.
Auteurs : Igor N. Sergeev [États-Unis] ; Shiming Li ; Chi-Tang Ho ; Nancy E. Rawson ; Slavik DushenkovSource :
- Journal of agricultural and food chemistry [ 1520-5118 ] ; 2009.
English descriptors
- KwdEn :
- 3T3-L1 Cells, Adipocytes (drug effects), Animals, Apoptosis (drug effects), Calcium (analysis), Calcium (physiology), Citrus sinensis (chemistry), Flavones (isolation & purification), Flavones (pharmacology), Flavonoids (isolation & purification), Flavonoids (pharmacology), Fruit (chemistry), Luteolin (isolation & purification), Luteolin (pharmacology), Mice.
- MESH :
- chemical , analysis : Calcium.
- chemistry : Citrus sinensis, Fruit.
- drug effects : Adipocytes, Apoptosis.
- chemical , isolation & purification : Flavones, Flavonoids, Luteolin.
- chemical , pharmacology : Flavones, Flavonoids, Luteolin.
- chemical , physiology : Calcium.
- 3T3-L1 Cells, Animals, Mice.
Abstract
Induction of apoptosis is an emerging strategy for the prevention and treatment of obesity because removal of adipocytes via apoptosis will result in reducing body fat and may help to maintain a long-lasting weight loss. Our previous studies have shown that a sustained increase in intracellular Ca(2+) triggers apoptosis in various cell types via activation of Ca(2+)-dependent proteases and that the apoptosis-inducing effect of polymethoxyflavones (PMFs) in cancer cells is mediated through Ca(2+) signaling. This paper reports that PMFs induce apoptosis in mature mouse 3T3-L1 adipocytes via activation of Ca(2+)-dependent calpain and Ca(2+)/calpain-dependent caspase-12. Treatment of adipocytes with PMFs evoked, in a concentration- and time-dependent fashion, sustained increase in the basal level of intracellular Ca(2+). The increase in Ca(2+) was associated with induction of apoptosis and activation of mu-calpain and caspase-12. Apoptosis-inducing activity of hydroxylated PMFs was significantly higher than that of the corresponding nonhydroxylated compounds. These results demonstrate that the apoptotic molecular targets activated by PMFs in adipocytes are Ca(2+)-dependent calpain and caspase-12. The findings obtained provide rationale for evaluating the role of PMFs in the prevention and treatment of obesity.
DOI: 10.1021/jf901071k
PubMed: 19522510
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pubmed:19522510Le document en format XML
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<author><name sortKey="Sergeev, Igor N" sort="Sergeev, Igor N" uniqKey="Sergeev I" first="Igor N" last="Sergeev">Igor N. Sergeev</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Nutrition, Food Science, South Dakota State University, Brookings, South Dakota 57007, USA. igor.sergeev@sdstate.edu</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Nutrition, Food Science, South Dakota State University, Brookings, South Dakota 57007</wicri:regionArea>
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<author><name sortKey="Li, Shiming" sort="Li, Shiming" uniqKey="Li S" first="Shiming" last="Li">Shiming Li</name>
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<author><name sortKey="Ho, Chi Tang" sort="Ho, Chi Tang" uniqKey="Ho C" first="Chi-Tang" last="Ho">Chi-Tang Ho</name>
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<author><name sortKey="Rawson, Nancy E" sort="Rawson, Nancy E" uniqKey="Rawson N" first="Nancy E" last="Rawson">Nancy E. Rawson</name>
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<author><name sortKey="Dushenkov, Slavik" sort="Dushenkov, Slavik" uniqKey="Dushenkov S" first="Slavik" last="Dushenkov">Slavik Dushenkov</name>
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<author><name sortKey="Ho, Chi Tang" sort="Ho, Chi Tang" uniqKey="Ho C" first="Chi-Tang" last="Ho">Chi-Tang Ho</name>
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<author><name sortKey="Rawson, Nancy E" sort="Rawson, Nancy E" uniqKey="Rawson N" first="Nancy E" last="Rawson">Nancy E. Rawson</name>
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<term>Calcium (analysis)</term>
<term>Calcium (physiology)</term>
<term>Citrus sinensis (chemistry)</term>
<term>Flavones (isolation & purification)</term>
<term>Flavones (pharmacology)</term>
<term>Flavonoids (isolation & purification)</term>
<term>Flavonoids (pharmacology)</term>
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<term>Apoptosis</term>
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<term>Flavonoids</term>
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<front><div type="abstract" xml:lang="en">Induction of apoptosis is an emerging strategy for the prevention and treatment of obesity because removal of adipocytes via apoptosis will result in reducing body fat and may help to maintain a long-lasting weight loss. Our previous studies have shown that a sustained increase in intracellular Ca(2+) triggers apoptosis in various cell types via activation of Ca(2+)-dependent proteases and that the apoptosis-inducing effect of polymethoxyflavones (PMFs) in cancer cells is mediated through Ca(2+) signaling. This paper reports that PMFs induce apoptosis in mature mouse 3T3-L1 adipocytes via activation of Ca(2+)-dependent calpain and Ca(2+)/calpain-dependent caspase-12. Treatment of adipocytes with PMFs evoked, in a concentration- and time-dependent fashion, sustained increase in the basal level of intracellular Ca(2+). The increase in Ca(2+) was associated with induction of apoptosis and activation of mu-calpain and caspase-12. Apoptosis-inducing activity of hydroxylated PMFs was significantly higher than that of the corresponding nonhydroxylated compounds. These results demonstrate that the apoptotic molecular targets activated by PMFs in adipocytes are Ca(2+)-dependent calpain and caspase-12. The findings obtained provide rationale for evaluating the role of PMFs in the prevention and treatment of obesity.</div>
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