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Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPAR [Formula: see text] Expression and Activation in Differentiating Mesenchymal Stem Cells
Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesyla...
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Formato: | Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2220071/ https://www.ncbi.nlm.nih.gov/pubmed/18274630 http://dx.doi.org/10.1155/2007/81654 |
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author | Rivas, Daniel Akter, Rahima Duque, Gustavo |
author_facet | Rivas, Daniel Akter, Rahima Duque, Gustavo |
author_sort | Rivas, Daniel |
collection | PubMed |
description | Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPAR [Formula: see text] 2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPAR [Formula: see text] , and SREBP-1 were determined by western blot. Finally, DNA binding PPAR [Formula: see text] activity was determined using an ELISA-based PPAR [Formula: see text] activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPAR [Formula: see text] expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPAR [Formula: see text] activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPAR [Formula: see text] expression and activity. |
format | Text |
id | pubmed-2220071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-22200712008-02-14 Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPAR [Formula: see text] Expression and Activation in Differentiating Mesenchymal Stem Cells Rivas, Daniel Akter, Rahima Duque, Gustavo PPAR Res Research Article Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPAR [Formula: see text] 2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPAR [Formula: see text] , and SREBP-1 were determined by western blot. Finally, DNA binding PPAR [Formula: see text] activity was determined using an ELISA-based PPAR [Formula: see text] activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPAR [Formula: see text] expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPAR [Formula: see text] activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPAR [Formula: see text] expression and activity. Hindawi Publishing Corporation 2007 2007-12-09 /pmc/articles/PMC2220071/ /pubmed/18274630 http://dx.doi.org/10.1155/2007/81654 Text en Copyright © 2007 Daniel Rivas et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Rivas, Daniel Akter, Rahima Duque, Gustavo Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPAR [Formula: see text] Expression and Activation in Differentiating Mesenchymal Stem Cells |
title | Inhibition of Protein Farnesylation Arrests Adipogenesis
and Affects PPAR [Formula: see text] Expression and Activation in
Differentiating Mesenchymal Stem Cells |
title_full | Inhibition of Protein Farnesylation Arrests Adipogenesis
and Affects PPAR [Formula: see text] Expression and Activation in
Differentiating Mesenchymal Stem Cells |
title_fullStr | Inhibition of Protein Farnesylation Arrests Adipogenesis
and Affects PPAR [Formula: see text] Expression and Activation in
Differentiating Mesenchymal Stem Cells |
title_full_unstemmed | Inhibition of Protein Farnesylation Arrests Adipogenesis
and Affects PPAR [Formula: see text] Expression and Activation in
Differentiating Mesenchymal Stem Cells |
title_short | Inhibition of Protein Farnesylation Arrests Adipogenesis
and Affects PPAR [Formula: see text] Expression and Activation in
Differentiating Mesenchymal Stem Cells |
title_sort | inhibition of protein farnesylation arrests adipogenesis
and affects ppar [formula: see text] expression and activation in
differentiating mesenchymal stem cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2220071/ https://www.ncbi.nlm.nih.gov/pubmed/18274630 http://dx.doi.org/10.1155/2007/81654 |
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