Overexpression of heme oxygenase (HO)-1 renders jurkat T cells resistant to Fas-mediated apoptosis: involvement of iron released by HO-1

Choi, Byung-Min; Pae, Hyun‐Ock; Jeong, Young-Ran; Oh, Gi‐Su; Jun, Chang‐Duk; Kim, Bok-Ryang; Kim, Young‐Myeong; Chung, Hun‐Taeg

doi:10.1016/j.freeradbiomed.2004.01.004

Cited by 64 publications

(32 citation statements)

References 55 publications

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“…Iron released by HO-1 may reduce apoptosis (14), possibly through increases in ferritin (3,46). Additionally, bilirubin (and its precursor biliverdin) are known to reduce oxidative stress (53), inflammation (18), and apoptosis (26).…”

Section: Discussionmentioning

confidence: 99%

Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion

Burger¹,

Xiang²,

Hammoud³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol 296: H84 -H93, 2009; doi:10.1152/ajpheart.00372.2008.-We have recently demonstrated that erythropoietin (EPO) protects cardiomyocytes from apoptosis during myocardial ischemia-reperfusion (I/R). The objective of the present study was to investigate the role of heme oxygenase (HO)-1 in the antiapoptotic effects of EPO. Primary cultures of neonatal mouse cardiomyocytes were subjected to anoxiareoxygenation (A/R). Pretreatment with EPO significantly reduced apoptosis in A/R-treated cells. This reduction in apoptosis was preceded by an increase in the mRNA and protein expression of HO-1. Selective inhibition of HO-1 using chromium mesoporphyrin (CrMP) significantly diminished the ability of EPO to inhibit apoptosis. Cotreatment of EPO with SB-202190, an inhibitor of p38 activation, blocked the EPO-mediated HO-1 expression and antiapoptotic effects, suggesting a p38-dependent mechanism. The in vivo significance of p38 and HO-1 as mediators of EPO's cardioprotection was investigated in mice subjected to myocardial I/R. Pretreatment with EPO decreased infarct size as well as I/R-induced apoptosis in wild-type mice. However, these effects were significantly diminished in HO-1 Ϫ/Ϫ mice. Furthermore, EPO given during ischemia reduced infarct size in mice subjected to I/R, and this effect was blocked by CrMP treatment in wild-type mice. Moreover, inhibition of p38 diminished the cardioprotective effects of EPO. We conclude that upregulation of HO-1 expression via p38 signaling contributes to EPO-mediated cardioprotection during myocardial I/R. myocyte; apoptosis; myocardial infarction; p38 ERYTHROPOIETIN (EPO) has been shown to protect the heart from ischemia-reperfusion (I/R) injury (8, 11). After myocardial infarction, EPO improves cardiac function and reduces ventricular remodeling (41). Our laboratory has demonstrated an important role of protein kinase B (Akt) and endothelial nitric oxide (NO) synthase (eNOS)-derived NO production in the antiapoptotic effects of EPO during myocardial I/R (7). However, since EPO is known to activate multiple intracellular signaling pathways, it is possible that additional mechanisms are involved in EPO's cardioprotective effects.Heme oxygenase (HO) is the rate-limiting enzyme responsible for the breakdown of heme into free ferrous iron, carbon monoxide (CO), and biliverdin, which is ultimately converted to bilirubin. There are three known isoforms of HO. HO-1 is expressed ubiquitously and is inducible. HO-2 is constitutively active and expressed primarily in the brain and testes, and HO-3 is constitutively active as well, but less efficient than the other two oxygenases (47). HO-1 and its byproducts play an important role in regulating cardiomyocyte survival. To this end, the cardiac-specific overexpression of HO-1 reduces oxidative stress and cell death in the heart after myocardial I/R (49). Additionally, HO-1 is known to have a protective ...

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Section: Discussionmentioning

confidence: 99%

Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion

Burger¹,

Xiang²,

Hammoud³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Heme oxygenase-1 (HO-1) is induced by oxidative stress (reviewed in [13]) and can inhibit apoptosis in several cell types such as T cells [14,15], endothelial cells [16] Page 5 of 38 A c c e p t e d M a n u s c r i p t 5 and enterocytes [17]. In human OA chondrocytes, HO-1 induction by low doses of sodium nitroprusside has been shown to protect against apoptosis induced by high doses of this agent [18].…”

Section: Introductionmentioning

confidence: 99%

Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes

Megías

Guillén²,

Clérigues³

et al. 2009

Biochemical Pharmacology

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“…However, growing evidence has shown that human Treg constitutively express HO-1 and that HO-1 inhibits T-cell proliferation [26]. Over-expression of HO-1 further renders T-cells resistant to Fas-mediated apoptosis [27]. Most recently, FoxP3, which encodes a forkhead/winged-helix transcription repressor specifically expressed in Treg, has been shown to induce HO-1 expression [28].…”

Section: Introductionmentioning

confidence: 99%

CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

2007

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Regulatory T-cells play an important role in the regulation of the immune response and the mediation of dominant immunologic tolerance. We have previously shown that these cells are elevated in tumors and blood of patients with glioblastoma multiforme. Heme oxygenase-1, a rate-limiting enzyme in heme catabolism, has also been shown to accumulate during glioma progression and to play a critical role in FoxP3 mediated immune suppression. In this study, we investigated the correlation between FoxP3 and HO-1 expression in patients with various grades of astrocytoma (WHO grade II-IV). Using qualitative and quantitative reverse transcriptase-polymerase chain reaction and quantitative flow cytometry analyses, we analyzed FoxP3 and HO-1 expression in 19 patients with different grades of astrocytoma. We observed the highest level of FoxP3 expression in patients with grade IV tumors (11.54 ± 1.95%) vs. grade III (6.74 ± 0.19%) or grade II (2.53 ± 0.11%) (P < 0.05). Moreover, in grade IV tumors, the frequency of HO-1 mRNA expression in CD4 + CD25 + cells was 11.8 ± 2.45% vs. 7.42 ± 0.31% in grade III and 2.33 ± 0.12% in grade II. Tumor infiltrating Treg stained positively with anti-HO-1 antibody. The expression of HO-1 correlated with CD4 + CD25 + FoxP3 + infiltration (r = 0.966). Our results confirm that HO-1 expressing Treg accumulate during glioma progression. This study also suggests that HO-1 mRNA expression is linked to the induction of Foxp3 in CD4 + CD25 + glioma infiltrating Treg. These findings support the suppressive role played by regulatory T-cells in the growth of malignant brain tumors.

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Overexpression of heme oxygenase (HO)-1 renders jurkat T cells resistant to Fas-mediated apoptosis: involvement of iron released by HO-1

Cited by 64 publications

References 55 publications

Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion

Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion

Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes

CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

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