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Curcumin alters MAPK intensity and duration in 3T3‐L1 preadipocytes that correlates with diverse cellular function
Publication year - 2008
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.22.1_supplement.700.33
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , kinase , microbiology and biotechnology , curcumin , apoptosis , phosphatase , mitogen activated protein kinase , phosphorylation , cell growth , protein kinase a , chemistry , biology , biochemistry
We have shown that curcumin, a polyphenolic phytochemical, arrests preadipocyte proliferation during late G 1 phase in a dose‐dependent manner with maximal growth suppression observed at 20 μM. Concentrations greater than 30 μM, were found to initiate apoptotic signaling and cell death. To elucidate the role of curcumin in 3T3‐L1 preadipocytes, we examined the mitogen‐activated protein kinases (MAPKs), a family of kinases that are known to regulate proliferation, differentiation, stress, inflammation, and apoptosis. Previous reports attribute this functional diversity with the magnitude and duration of MAPK activity. We show that ERK1/2, p38, and JNK were transiently activated via phosphorylation during early (<1hr) preadipocyte differentiation without change in protein abundance. MAPK activation was immediately followed by transient expression of the MAPK phosphatase, MKP‐1, which has been shown to dephosphorylate all MAPK family members. In the absence of proliferation, curcumin transiently induced the activity of all three MAPKs. Treating preadipocytes with the differentiation cocktail in the presence of curcumin resulted in robust and persistent activation of all three MAPKs as well as MKP‐1 in a concentration‐dependent manner, with toxic doses (>30μM) resulting in prolonged MAPK activity exceeding 20 hrs post‐stimulation. These data support the hypothesis that early, transient activation of MAPKs signals cell survival while sustained, persistent MAPK activity promotes cell‐cycle arrest and/or apoptosis. Supported by NIH (5R21DK072067‐02).