Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72

Valen, Guro; Kawakami, Tomohiro; Tähepõld, Peeter; Dumitrescu, A; Löwbeer, Christian; Vaage, Jarle

doi:10.1152/ajpheart.2000.279.2.h836

Cited by 61 publications

(37 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The enzyme 11␤-HSD converts 11-keto-steroids into active glucocorticoids and therefore amplifies the action of glucocorticoids. Despite these undesirable effects in vivo and in vitro, corticosteroids have been found to protect the heart from ischemia and reperfusion injury in animal models (Libby et al, 1973;Spath et al, 1974;Busuttil and George, 1978;Valen et al, 2000). Whether corticosteroids can initiate an antiapoptotic response in vivo in mediating the cardiac protective effect remains to be investigated.…”

Section: Corticosteroid Induced Cytoprotection In Cardiomyocytes 1871mentioning

confidence: 99%

Corticosteroids Inhibit Cell Death Induced by Doxorubicin in Cardiomyocytes: Induction of Antiapoptosis, Antioxidant, and Detoxification Genes

et al. 2005

View full text Add to dashboard Cite

Psychological or physical stress induces an elevation of corticosteroids in the circulating system. We report here that corticosterone (CT) protects cardiomyocytes from apoptotic cell death induced by doxorubicin (Dox), an antineoplastic drug known to induce cardiomyopathy possibly through reactive oxygen species production. The cytoprotection induced by CT is within the range of physiologically relevant doses. The lowest dose tested, 0.1 M (or 3.5 g/dl), inhibited apoptosis by approximately 25% as determined by caspase activity. With 1 M CT, cardiomyocytes gain a cytoprotective effect after 8 h of incubation and remain protected for at least 72 h. Hydrocortisone, cortisone, dexamethasone, and aldosterone but not androstenedione or cholesterol also induced cytoprotection. Analyses of 20,000 gene expression sequences using Affymetrix high-density oligonucleotide array found that CT caused up-regulation of 140 genes and down-regulation of 108 genes over 1.5-fold. Among the up-regulated genes are bcl-xL, metallothioneins, glutathione peroxidase-3, and glutathione Stransferases. Western blot analyses revealed that CT induced an elevation of bcl-xL but not bcl-2 or proapoptotic factors bax, bak, and bad. Inhibiting the expression of bcl-xL reduced the cytoprotective effect of CT. Our data suggest that CT induces a cytoprotective effect on cardiomyocytes in association with reprogramming gene expression and induction of bcl-xL gene.

show abstract

Section: Corticosteroid Induced Cytoprotection In Cardiomyocytes 1871mentioning

confidence: 99%

Corticosteroids Inhibit Cell Death Induced by Doxorubicin in Cardiomyocytes: Induction of Antiapoptosis, Antioxidant, and Detoxification Genes

et al. 2005

View full text Add to dashboard Cite

show abstract

“…These acute effects contribute to an adaptive response, at least in the short term. For example, the cardioprotective effects of glucocorticoids in the acute setting of myocardial ischemia/reperfusion have been experimentally demonstrated in animals (2)(3)(4)(5) and in humans (6). The beneficial effect of glucocorticoids has been attributed mostly to their ability to limit the acute inflammatory response associated with acute myocardial infarction: glucocorticoids act on leukocytes and endothelial cells to attenuate leukocyte-endothelial cell interactions (7) and to reduce the generation and release of proinflammatory cytokines and mediators (8).…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase–derived PGD2 biosynthesis

Tokudome

Sano²,

Shinmura³

et al. 2009

J. Clin. Invest.

View full text Add to dashboard Cite

Lipocalin-type prostaglandin D synthase (L-PGDS), which was originally identified as an enzyme responsible for PGD 2 biosynthesis in the brain, is highly expressed in the myocardium, including in cardiomyocytes. However, the factors that control expression of the gene encoding L-PGDS and the pathophysiologic role of L-PGDS in cardiomyocytes are poorly understood. In the present study, we demonstrate that glucocorticoids, which act as repressors of prostaglandin biosynthesis in most cell types, upregulated the expression of L-PGDS together with cytosolic calcium-dependent phospholipase A2 and COX2 via the glucocorticoid receptor (GR) in rat cardiomyocytes. Accordingly, PGD 2 was the most prominently induced prostaglandin in vivo in mouse hearts and in vitro in cultured rat cardiomyocytes after exposure to GR-selective agonists. In isolated Langendorff-perfused mouse hearts, dexamethasone alleviated ischemia/reperfusion injury. This cardioprotective effect was completely abrogated by either pharmacologic inhibition of COX2 or disruption of the gene encoding L-PGDS. In in vivo ischemia/reperfusion experiments, dexamethasone reduced infarct size in wild-type mice. This cardioprotective effect of dexamethasone was markedly reduced in L-PGDS-deficient mice. In cultured rat cardiomyocytes, PGD 2 protected against cell death induced by anoxia/reoxygenation via the D-type prostanoid receptor and the ERK1/2-mediated pathway. Taken together, these results suggest what we believe to be a novel interaction between glucocorticoid-GR signaling and the cardiomyocyte survival pathway mediated by the arachidonic acid cascade.

show abstract

“…Besides the classic activation of the SPR with heat or hyperthermia, also called heat shock (31,33), SPR has been shown to be induced after various stimuli, e.g., corticosteroids (41,42), catecholamines (19), and oxidative stress (24,45), as well as after specific pharmacological treatments like 17-allylamino-17-demethoxy-geldanamycin (17-AAG) (38). Therefore, it is not surprising that SPR has been shown to be activated under certain clinical situations such as sepsis and septic and hemorrhagic shock (10,37,40).…”

mentioning

confidence: 99%

Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury

Ganter¹,

Ware²,

Howard³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Previous studies have shown that heat shock protein 72 (Hsp72) is found in the extracellular space (eHsp72) and that eHsp72 has potent immunomodulatory effects. However, whether eHsp72 is present in the distal air spaces and whether eHsp72 could modulate removal of alveolar edema is unknown. The first objective was to determine whether Hsp72 is released within air spaces and whether Hsp72 levels in pulmonary edema fluid would correlate with the capacity of the alveolar epithelium to remove alveolar edema fluid in patients with ALI/ARDS. Patients with hydrostatic edema served as controls. The second objective was to determine whether activation of the stress protein response (SPR) caused the release of Hsp72 into the extracellular space in vivo and in vitro and to determine whether SPR activation and/or eHsp72 itself would prevent the IL-1β-mediated inhibition of the vectorial fluid transport across alveolar type II cells. We found that eHsp72 was present in plasma and pulmonary edema fluid of ALI patients and that eHsp72 was significantly higher in pulmonary edema fluid from patients with preserved alveolar epithelial fluid clearance. Furthermore, SPR activation in vivo in mice and in vitro in lung endothelial, epithelial, and macrophage cells caused intracellular expression and extracellular release of Hsp72. Finally, SPR activation, but not eHsp72 itself, prevented the decrease in alveolar epithelial ion transport induced by exposure to IL-1β. Thus SPR may protect the alveolar epithelium against oxidative stress associated with experimental ALI, and eHsp72 may serve as a marker of SPR activation in the distal air spaces of patients with ALI.Keywords pulmonary edema; alveolar fluid clearance; heat shock response; respiratory distress syndrome; heat shock protein 70 ACUTE LUNG INJURY (ALI) is a common cause of acute respiratory failure in critically ill patients. The early phase of ALI is characterized by the accumulation and activation of inflammatory cells (neutrophils and macrophages) within the distal air spaces that release high levels of oxidant species (46). Alveolar epithelial and lung endothelial injury leads to increased permeability, Copyright © 2006 the American Physiological SocietyAddress for reprint requests and other correspondence: M. T. Ganter, Dept. of Anesthesia and Perioperative Care, San Francisco General Hospital, 1001 Potrero Ave., Rm. San Francisco, CA 94110 (mt.ganter@gmail.com).. NIH Public AccessAuthor Manuscript Am J Physiol Lung Cell Mol Physiol. Author manuscript; available in PMC 2009 October 21. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript pulmonary edema, and acute respiratory failure. An important mechanism to prevent alveolar flooding is the maintenance or upregulation of lung alveolar fluid clearance (AFC), requiring an intact alveolar epithelium (47). However, AFC has been shown to be impaired in the majority of ALI patients, and an impaired AFC was associated with worse clinical outcomes (47).Heat shock or stress proteins (Hsp) are a ...

show abstract

Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72

Cited by 61 publications

References 20 publications

Corticosteroids Inhibit Cell Death Induced by Doxorubicin in Cardiomyocytes: Induction of Antiapoptosis, Antioxidant, and Detoxification Genes

Corticosteroids Inhibit Cell Death Induced by Doxorubicin in Cardiomyocytes: Induction of Antiapoptosis, Antioxidant, and Detoxification Genes

Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase–derived PGD2 biosynthesis

Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury

Contact Info

Product

Resources

About