Inhibition of adipogenesis and leptin production in 3T3-L1 adipocytes by a derivative of meridianin C

Title
Inhibition of adipogenesis and leptin production in 3T3-L1 adipocytes by a derivative of meridianin C
Author(s)
박유경[박유경]이태윤최종순[최종순]홍석봉[홍석봉]이진호[이진호]박종욱[박종욱]장병철[장병철]
Keywords
ADIPOSE-TISSUE; C/EBP-ALPHA; KINASE INHIBITORS; GENE-EXPRESSION; INSULIN ACTION; PPAR-GAMMA; IN-VITRO; DIFFERENTIATION; PROTEIN; ADIPONECTIN
Issue Date
201410
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.452, no.4, pp.1078 - 1083
Abstract
Meridianin C, a marine alkaloid, is a potent protein kinase inhibitor and has anti-cancer activity. We have recently developed a series of meridianin C derivatives (compound 7a-7j) and reported their proviral integration Moloney Murine Leukemia Virus (pim) kinases' inhibitory and anti-proliferative effects on human leukemia cells. Here we investigated the effect of these meridianin C derivatives on adipogenesis. Strikingly, among the derivatives tested, compound 7b most strongly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. However, meridianin C treatment was largely cytotoxic to 3T3-L1 adipocytes. On mechanistic levels, compound 7b reduced not only the expressions of CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and fatty acid synthase (FAS) but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during adipocyte differentiation. Moreover, compound 7b repressed leptin, but not adiponectin, expression during adipocyte differentiation. Collectively, these findings demonstrate that a meridianin C derivative inhibits adipogenesis by down-regulating expressions and/or phosphorylations of C/EBP-alpha, PPAR-gamma, FAS, STAT-3 and STAT-5. (C) 2014 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/30694http://dx.doi.org/10.1016/j.bbrc.2014.09.050
ISSN
0006-291X
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의과대학 > 미생물학교실 > Articles
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