Glucocorticoids (GCs) are frequently prescribed pharmacological agents most notably for their immunosuppressant 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 receptor that translocates to the nuclei upon ligand binding and alters gene transcription. Among a long list of genes activated by GCs is the Glucocorticoid Induced Leucine Zipper (GILZ). Although GC induced GILZ expression has been well established in lymphocytes, little is known whether cardiomyocytes respond to GCs by inducing GILZ. Unlike lymphocytes, in which GCs induce apoptosis and GILZ mediates GC induced apoptosis, cardiomyocytes respond to GCs by gaining resistance against apoptosis. We determined GILZ expression pattern in cardiomyocytes in vivo and in vitro. Our data demonstrate GILZ induction in cardiomyocytes both in vivo and in vitro by GCs and point to H9C2 cell line as a valid model for studying the biological function of GILZ in cardiomyocytes. I have also determined GILZ functions as GC induced cytoprotective protein against the known cardiac toxicant Doxorubicin. Finally I have determined GILZ stabilizes Bcl-xL pro-survival protein, providing a possible mechanism of cytoprotection in cardiomyocytes.
|Advisor:||Chen, Qin M.|
|Commitee:||Bloom, John W., Larson, Douglas F., Vanderah, Todd W., Wondrak, Georg|
|School:||The University of Arizona|
|School Location:||United States -- Arizona|
|Source:||DAI-B 73/09(E), Dissertation Abstracts International|
|Subjects:||Toxicology, Surgery, Pharmacology|
|Keywords:||Cardiomyocytes, Corticosterone, Dexamethasone, Doxorubicin, Glucocorticoids, Primary neonatal cardiomyocytes|
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