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PMID: 7479942 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 24 ·1995-11-21 ·Pages 11086-90

Yeh WC, Bierer BE, McKnight SL

Abstract

Differentiating 3T3-L1 cells express an immunophilin early during the adipocyte conversion program as described in this issue [Yeh, W.-C., Li, T.-K., Bierer, B. E. & McKnight, S. L. (1995) Proc. Natl. Acad. Sci. USA 92, 11081-11085]. The temporal expression profile of this protein, designated FK506-binding protein (FKBP) 51, is concordant with the clonal-expansion period undertaken by 3T3-L1 cells after exposure to adipogenic hormones. Having observed FKBP51 synthesis early during adipogenesis, we tested the effects of three immunosuppressive drugs--cyclosporin A, FK506, and rapamycin--on the terminal-differentiation process. Adipocyte conversion was not affected by either cyclosporin A or FK506 and yet was significantly reduced by rapamycin at drug concentrations as low as 10 nM. Clonal expansion was impeded in drug-treated cultures, as was the accumulation of cytoplasmic lipid droplets normally seen late during differentiation. Rapamycin treatment likewise inhibited the expression of CCAAT/enhancer binding protein alpha, a transcription factor required for 3T3-L1 cell differentiation. All three of these effects were reversed by high FK506 concentrations, indicating that the operative inhibitory event was mediated by an immunophilin-rapamycin complex.

MeSH Terms
3T3 Cells Adipocytes/cytology Animals CCAAT-Enhancer-Binding Proteins Cell Differentiation/drug effects Clone Cells/drug effects Cyclosporine/pharmacology DNA-Binding Proteins/metabolism Gene Expression/drug effects Immunosuppressive Agents/pharmacology Mice Nuclear Proteins/metabolism Polyenes/antagonists & inhibitors,pharmacology RNA, Messenger/genetics Signal Transduction/drug effects Sirolimus Tacrolimus/pharmacology
Chemicals
CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Immunosuppressive Agents Nuclear Proteins Polyenes RNA, Messenger Cyclosporine Sirolimus Tacrolimus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yeh W C
Johns Hopkins University, Baltimore, MD 21205, USA.
Bierer B E
McKnight S L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.24.11086
Published
1995-11-21
Pages
11086-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40576
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.24.11086 PMC Full Text View journal details
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