Proprotein convertases are important mediators of the adipocyte differentiation of mouse 3T3-L1 cells.
Mouse 3T3-L1 cells are widely used to study adipocyte differentiation in vitro. When treated with insulin, dexamethasone and isobutylmethylxanthine these fibroblastic cells differentiate into round triglyceride-rich adipocytes. Because several proteins implicated in adipocyte differentiation (e.g. type 1 IGF receptors) are proteolytically activated by endoproteinases of the proprotein convertase family, we sought to determine whether these endoproteinases are crucial for adipose conversion. In this study, we show that expression of the proprotein convertases PACE4, PC7 and furin increases when 3T3-L1 cells are induced to differentiate into adipocytes. The differentiation was blocked in transfected cells expressing alpha1-antitrypsin Portland or in normal cells pre-treated with the synthetic inhibitor decanoyl-RVKR-chloromethylketone. Both inhibitors are known to specifically inactivate proprotein convertases. The block was associated with impaired proteolytic activation of proIGF-1 receptor, absence of induction of the adipogenic transcriptional factor PPARgamma and marked reduction of the nuclear translocation of the C/EBPbeta factor. Taken together, these data constitute evidence that proprotein convertases are crucial mediators of adipogenesis.
Croissandeau
Gilles
G
Diseases of Aging Program, Ottawa Health Research Institute at Ottawa Hospital, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4K9, Canada.
Basak
Ajoy
A
Seidah
Nabil G
NG
Chrétien
Michel
M
Mbikay
Majambu
M
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D011416:Complement Factor D; D045683:Furin; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D043484:Proprotein Convertases; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism; D013381:Subtilisins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; C497250:Ddit3 protein, mouse; D011480:Protease Inhibitors; D011498:Protein Precursors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C119953:pro-insulin-like growth factor I; D051742:Transcription Factor CHOP; D007334:Insulin-Like Growth Factor I; C513086:Pcsk6 protein, mouse; C490930:Pcsk7 protein, mouse; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; D011416:Complement Factor D; C493491:complement factor D, mouse; D045683:Furin