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| Content Provider | Springer Nature Link |
|---|---|
| Author | Aguilar, David C. Strom, Josh Xu, Beibei Kappeler, Kyle Chen, Qin M. |
| Copyright Year | 2012 |
| Abstract | Glucocorticoids (GCs) are frequently prescribed pharmacological agents most notably for their immunosuppressive effects. Endogenous GCs mediate biological processes such as energy metabolism and tissue development. At the cellular level, GCs bind to the glucocorticoid receptor (GR), a cytosolic protein that translocates to the nuclei and functions to alter transcription upon ligand binding. Among a long list of genes activated by GCs is the glucocorticoid-induced leucine zipper (GILZ). GC-induced GILZ expression has been well established in lymphocytes and mediates GC-induced apoptosis. Unlike lymphocytes, cardiomyocytes respond to GCs by gaining resistance against apoptosis. We determined GILZ expression in cardiomyocytes in vivo and in vitro. Expression of GILZ in mouse hearts as a result of GC administration was confirmed by Western blot analyses. GCs induced dose- and time-dependent elevation of GILZ expression in primary cultured rat cardiomyocytes, with dexamethasone (Dex) as low as 0.1 μM being effective. Time course analysis indicated that GILZ protein levels increased at 8 h and peaked at 48 h after exposure to 1 μM Dex. H9c2(2-1) cell line showed a similar response of GILZ induction by Dex as primary cultured rat cardiomyocytes, providing a convenient model for studying the biological significance of GILZ expression. With corticosterone (CT), an endogenous form of corticosteroids in rodents, 0.1–2.5 μM was found to induce GILZ in H9c2(2-1) cells. Time course analysis with 1 μM CT indicated induction of GILZ at 6 h with peak expression at 18 h. Inhibition of the GR by mifepristone led to blunting of GILZ induction by GCs. Our data demonstrate GILZ induction in cardiomyocytes both in vivo and in vitro by GCs, pointing to H9c2(2-1) cells as a valid model for studying the biological function of GILZ in cardiomyocytes. |
| Starting Page | 91 |
| Ending Page | 99 |
| Page Count | 9 |
| File Format | |
| ISSN | 15307905 |
| Journal | Cardiovascular Toxicology |
| Volume Number | 13 |
| Issue Number | 2 |
| e-ISSN | 15590259 |
| Language | English |
| Publisher | Humana Press Inc |
| Publisher Date | 2012-10-23 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Glucocorticoid-induced leucine zipper Glucocorticoids H9c2(2-1) cells neonatal cardiomyocytes Pharmacology/Toxicology Cardiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Toxicology Cardiology and Cardiovascular Medicine |
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