GILZ: A Novel Glucocorticoid Induced Cytoprotective Protein in Cardiomyocytes

Persistent Link:
http://hdl.handle.net/10150/228177
Title:
GILZ: A Novel Glucocorticoid Induced Cytoprotective Protein in Cardiomyocytes
Author:
Aguilar, David Christopher
Issue Date:
2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
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.
Type:
text; Electronic Dissertation
Keywords:
doxorubicin; glucocorticoid induced leucine zipper; H9C2 rat cardiomyocytes; primary neonatal cardiomyocytes; Medical Pharmacology; corticosterone; dexamethasone
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Medical Pharmacology
Degree Grantor:
University of Arizona
Advisor:
Chen, Qin M.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleGILZ: A Novel Glucocorticoid Induced Cytoprotective Protein in Cardiomyocytesen_US
dc.creatorAguilar, David Christopheren_US
dc.contributor.authorAguilar, David Christopheren_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractGlucocorticoids (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.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectdoxorubicinen_US
dc.subjectglucocorticoid induced leucine zipperen_US
dc.subjectH9C2 rat cardiomyocytesen_US
dc.subjectprimary neonatal cardiomyocytesen_US
dc.subjectMedical Pharmacologyen_US
dc.subjectcorticosteroneen_US
dc.subjectdexamethasoneen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMedical Pharmacologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorChen, Qin M.en_US
dc.contributor.committeememberVanderah, Todd W.en_US
dc.contributor.committeememberLarson, Douglas F.en_US
dc.contributor.committeememberBloom, John W.en_US
dc.contributor.committeememberChen, Qin M.en_US
dc.contributor.committeememberWondrak, Georgen_US
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