title: Dexamethasone induces transcriptional activation of Bcl-xL gene and inhibits cardiac injury by myocardial ischemia.
abstract: Psychological or physical stress causes an elevation of glucocorticoids in the circulating system. Glucocorticoids regulate a variety of physiological functions, from energy metabolism and biochemical homeostasis to immune response. Synthetic steroids are among the most prescribed drugs for immune suppression and chemotherapy. While glucocorticoids are best known for inducing apoptosis in a number of cell types, we have found that corticosteroids at stress relevant levels protect cardiomyocytes from apoptosis. Current study addresses whether glucocorticoids inhibit cardiac injury in vivo. Adult male C57BL6 mice were administered with dexamethasone (20mg/kg, i.p.) or vehicle control 20 h prior to left anterior descending coronary artery occlusion surgery. Myocardial infarction was measured by triphenyl tetrazoliumchloride staining in tissue slices and by levels of cardiac Troponin (cTn I) in the blood. Treatment of dexamethasone markedly reduced infarct size (19.6 ± 4.3%, vs. 29.2 ± 4.9%, p<0.01) and cTn I level in the blood (3.83 ± 0.66 ng/ml vs. 5.62 ± 0.37 ng/ml, p<0.01). In studying the mechanism of such protection, we found that dexamethasone induces the expression of Bcl-xL gene in the myocardium. With cardiomyocytes in culture, glucocorticoids increased transcription of Bcl-xL gene as evidenced by Bcl-xL mRNA increase and promoter activation. The glucocorticoid receptor antagonist mifepristone prevented dexamethasone from inducing cardiac protection or Bcl-xL expression. Our data suggest that activation of glucocorticoid receptor can prevent cardiac injury through transcriptional activation of Bcl-xL gene.
authors: Department of Pharmacology, College of Medicine, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85724, United States.
authors: Beibei
authors: B
authors: Xu
authors: Joshua
authors: J
authors: Strom
authors: Qin M
authors: QM
authors: Chen
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006335:Heart Injuries / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000150:complications*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015533:Transcriptional Activation / Q000187:drug effects*; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D051020:bcl-X Protein; D003907:Dexamethasone