Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism
The PPARγ nuclear receptor regulates the expression of genes involved in lipid and carbohydrate metabolism, and it has protective effects in some patients with type 2 diabetes. Nevertheless, the therapeutic value of the PPARγ nuclear receptor protein is limited due to the secondary effects of some P...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sociedade Brasileira de Genética
2013-01-01
|
| Series: | Genetics and Molecular Biology |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572013000100020&lng=en&tlng=en |
| _version_ | 1811266946814967808 |
|---|---|
| author | Fernando Lizcano Diana Vargas |
| author_facet | Fernando Lizcano Diana Vargas |
| author_sort | Fernando Lizcano |
| collection | DOAJ |
| description | The PPARγ nuclear receptor regulates the expression of genes involved in lipid and carbohydrate metabolism, and it has protective effects in some patients with type 2 diabetes. Nevertheless, the therapeutic value of the PPARγ nuclear receptor protein is limited due to the secondary effects of some PPARγ ligands. Because the downstream effects of PPARγ are determined by the binding of specific cofactors that are mediated by ligand-induced conformational changes, we evaluated the differential effects of various ligands on the binding of certain cofactors associated with PPARγ. The ligands used were rosiglitazone for treating type 2 diabetes and telmisartan for treating arterial hypertension. Functional, phenotypic, and molecular studies were conducted on pre-adipocyte 3T3-L1 and functional studies in U2OS cells. The moderating influence of various cofactor families was evaluated using transient transfection assays. Our findings confirm that telmisartan has a partial modulating effect on PPARγ activity compared to rosiglitazone. The cofactors SRC1 and GRIP1 mediate the activity of telmisartan and rosiglitazone and partially determine the difference in their effects. Studying the modulating activity of these cofactors can provide interesting insights for developing new therapeutic approaches for certain metabolic diseases. |
| first_indexed | 2024-04-12T20:53:32Z |
| format | Article |
| id | doaj.art-6ec6db58d08a4bf68d1073a6aea77b56 |
| institution | Directory Open Access Journal |
| issn | 1678-4685 |
| language | English |
| last_indexed | 2024-04-12T20:53:32Z |
| publishDate | 2013-01-01 |
| publisher | Sociedade Brasileira de Genética |
| record_format | Article |
| series | Genetics and Molecular Biology |
| spelling | doaj.art-6ec6db58d08a4bf68d1073a6aea77b562022-12-22T03:17:03ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-46852013-01-01361134139S1415-47572013000100020Diverse coactivator recruitment through differential PPARγ nuclear receptor agonismFernando Lizcano0Diana Vargas1Universidad de La SabanaUniversidad de La SabanaThe PPARγ nuclear receptor regulates the expression of genes involved in lipid and carbohydrate metabolism, and it has protective effects in some patients with type 2 diabetes. Nevertheless, the therapeutic value of the PPARγ nuclear receptor protein is limited due to the secondary effects of some PPARγ ligands. Because the downstream effects of PPARγ are determined by the binding of specific cofactors that are mediated by ligand-induced conformational changes, we evaluated the differential effects of various ligands on the binding of certain cofactors associated with PPARγ. The ligands used were rosiglitazone for treating type 2 diabetes and telmisartan for treating arterial hypertension. Functional, phenotypic, and molecular studies were conducted on pre-adipocyte 3T3-L1 and functional studies in U2OS cells. The moderating influence of various cofactor families was evaluated using transient transfection assays. Our findings confirm that telmisartan has a partial modulating effect on PPARγ activity compared to rosiglitazone. The cofactors SRC1 and GRIP1 mediate the activity of telmisartan and rosiglitazone and partially determine the difference in their effects. Studying the modulating activity of these cofactors can provide interesting insights for developing new therapeutic approaches for certain metabolic diseases.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572013000100020&lng=en&tlng=enDNA binding proteins co-activatorgene expressiontranscriptiontelmisartan |
| spellingShingle | Fernando Lizcano Diana Vargas Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism Genetics and Molecular Biology DNA binding proteins co-activator gene expression transcription telmisartan |
| title | Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism |
| title_full | Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism |
| title_fullStr | Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism |
| title_full_unstemmed | Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism |
| title_short | Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism |
| title_sort | diverse coactivator recruitment through differential pparγ nuclear receptor agonism |
| topic | DNA binding proteins co-activator gene expression transcription telmisartan |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572013000100020&lng=en&tlng=en |
| work_keys_str_mv | AT fernandolizcano diversecoactivatorrecruitmentthroughdifferentialppargnuclearreceptoragonism AT dianavargas diversecoactivatorrecruitmentthroughdifferentialppargnuclearreceptoragonism |