Compound C inhibits clonal expansion of preadipocytes by increasing p21 level irrespectively of AMPK inhibition.
AMP-activated protein kinase (AMPK) activation inhibits adipocyte differentiation. This study investigated the effect of compound C (CC), a widely used AMPK inhibitor, on differentiation of 3T3-L1 preadipocytes. CC treatment blocked hormone-induced preadipocyte differentiation due to inhibition of mitotic clonal expansion, which was accompanied by the failure of degradation of p21, a cyclin-dependent kinase inhibitor. CC increased the level of p21 protein, but not its mRNA, in preadipocytes incubated in a hormone-free medium. Cycloheximide decreased the basal p21 level, which was inhibited by CC treatment, supporting the stabilization of p21 by CC. Treatment of AICAR or metformin, AMPK activators, failed to induce p21 or inhibit the ability of CC to increase p21 level. In conclusion, CC inhibits proliferation of preadipocytes as a consequence of an increase in p21 content, which might result from p21 stabilization, and the increase in p21 level by CC might not be associated with AMPK inhibition.
Nam
Minwoo
M
Innovative Drug Research Center for Metabolic and Inflammatory Diseases, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Sillimdong, Kwanak-gu, Seoul, Republic of Korea.
Lee
Woo Hyung
WH
Bae
Eun Ju
EJ
Kim
Sang Geon
SG
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013997:Time Factors
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin; D055372:AMP-Activated Protein Kinases