Carbon monoxide (CO)-releasing molecule-derived CO regulates tissue factor and plasminogen activator inhibitor type 1 in human endothelial cells

Maruyama, Keiko; Morishita, Eriko; Yuno, Takeo; Sekiya, Akiko; Asakura, Hitoshi; Ohtake, Shigeki; Yachie, Akihiro

doi:10.1016/j.thromres.2012.07.002

Cited by 23 publications

(11 citation statements)

References 38 publications

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“…Furthermore, it was shown that CORM-2 suppressed pro-thrombotic (tissue factor, TF) and anti-fibrynolytic (PAI-1) activities of the endothelium stimulated by inflammatory cytokines (TNF-α) and regulated activation of MAPKs and NF-kB signaling pathways [15]. However, the target responsible for the beneficial action of CO in the endothelium remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels

Kaczara

Motterlini

Rosen

et al. 2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Carbon monoxide (CO), a product of heme degradation by heme oxygenases, plays an important role in vascular homeostasis. Recent evidence indicates that mitochondria are among a number of molecular targets that mediate the cellular actions of CO. In the present study we characterized the effects of CO released from CORM-401 on mitochondrial respiration and glycolysis in intact human endothelial cells using electron paramagnetic resonance (EPR) oximetry and the Seahorse XF technology. We found that CORM-401 (10-100μM) induced a persistent increase in the oxygen consumption rate (OCR) that was accompanied by inhibition of glycolysis (extracellular acidification rate, ECAR) and a decrease in ATP-turnover. Furthermore, CORM-401 increased proton leak, diminished mitochondrial reserve capacity and enhanced non-mitochondrial respiration. Inactive CORM-401 (iCORM-401) neither induced mitochondrial uncoupling nor inhibited glycolysis, supporting a direct role of CO in the endothelial metabolic response induced by CORM-401. Interestingly, blockade of mitochondrial large-conductance calcium-regulated potassium ion channels (mitoBKCa) with paxilline abolished the increase in OCR promoted by CORM-401 without affecting ECAR; patch-clamp experiments confirmed that CO derived from CORM-401 activated mitoBKCa channels present in mitochondria. Conversely, stabilization of glycolysis by MG132 prevented CORM-401-mediated decrease in ECAR but did not modify the OCR response. In summary, we demonstrated in intact endothelial cells that CO induces a two-component metabolic response: uncoupling of mitochondrial respiration dependent on the activation of mitoBKCa channels and inhibition of glycolysis independent of mitoBKCa channels.

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Section: Introductionmentioning

confidence: 99%

Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels

Kaczara

Motterlini

Rosen

et al. 2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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“…The mechanisms through which the donor HO-1 A/A or A/T genotype (plausibly associated with the higher inducibility of HO-1) exerts its beneficial effects remains to be determined. HO-1 is only marginally produced in the resting state, but is rapidly and highly induced in response to various oxidative stresses (e.g., organ and tissue damage and infection), and acts as an anti-inflammatory and cytoprotective protein [7,[9][10][11]15,31,32]. Evidence of HO-1 induction improving the survival outcomes after allo-HSCT has been demonstrated in previous studies using mouse models [31,33].…”

Section: Discussionmentioning

confidence: 90%

“…Heme oxygenase-1 (HO-1), also known as a 32 kDa heat-shock protein, is an intracellular enzyme that catalyzes the degradation of heme into biliverdin, ferrous iron, and carbon monoxide (CO), with biliverdin being subsequently catabolized into bilirubin [7][8][9][10][11]. HO-1 is highly induced in response to various stress signals, such as free heme and hemoglobin, inflammatory cytokines, ischemia, endotoxins, irradiation, and mucosal damage [9][10][11][12][13][14][15][16]. HO-1 thus exerts cytoprotective effects on endothelial cells through ant-oxidative, anti-inflammatory, anti-apoptotic, and anti-thrombotic effects, which are coordinated with heme metabolites of CO and bilirubin.…”

Section: Introductionmentioning

confidence: 99%

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Horio

Morishita

Mizuno

et al. 2020

Cancers

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Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.

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“…Recently, transition metal carbonyls have been identified as the potential to facilitate the pharmaceutical use of CO by delivering it to the tissues and organs of interest 13, 26. Studies elucidated that CORM-2 suppressed LPS-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs), peripheral blood mononuclear cells (PBMCs) and macrophages 27, 28. Similarly, the results reported in our laboratory and others confirmed that CO derived from CORMs rescued mice from lethal sepsis induced by LPS or CLP 16-18.…”

Section: Discussionmentioning

confidence: 99%

A Novel Role of Exogenous Carbon Monoxide on Protecting Cardiac Function and Improving Survival against Sepsis via Mitochondrial Energetic Metabolism Pathway

Wang¹,

Qin²,

Qiu³

et al. 2014

Int. J. Biol. Sci.

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Septic cardiac dysfunction is the main cause of death in septic patients. Here we investigate whether exogenous carbon monoxide can protect cardiac function and improve survival against sepsis by interfering with mitochondrial energetic metabolism. Male C57BL/6 mice were subjected to cecal ligation and puncture to induce sepsis. Exogenous carbon monoxide delivered from Tricarbonyldichlororuthenium (II) dimer (carbon monoxide releasing molecule II, 8mg/kg) was used intravenously as intervention. We found that carbon monoxide significantly improved cardiac function (LVEF 80.26 ± 2.37% vs. 71.21 ± 1.37%, P < 0.001; LVFS 43.52 ± 1.92% vs. 34.93 ± 1.28%, P < 0.001) and increased survival rate of septic mice (63% vs. 25%, P < 0.01). This phenomenon might be owing to the beneficial effect of carbon monoxide on abolishing the elevation of cardiac enzyme activity, cytokines levels and apoptosis rate, then attenuating cardiac injury in septic mice. Meanwhile, carbon monoxide significantly reversed the loss of mitochondrial number, effectively inhibited cardiac mitochondrial damage in septic mice by modulating glucose uptake, adenosine triphosphate and lactate content. Furthermore upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A genes in cardiac tissue were revealed in septic mice treated with carbon monoxide. Taken together, the results indicate that exogenous carbon monoxide effectively modulated mitochondrial energetic metabolisms by interfering with expression of peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A genes, consequently exerted an important improvement in sepsis-induced cardiac dysfunction.

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Carbon monoxide (CO)-releasing molecule-derived CO regulates tissue factor and plasminogen activator inhibitor type 1 in human endothelial cells

Abstract: Introduction: Heme oxygenase-1 (HO-1) is the rate limiting enzyme that catalyzes the

Cited by 23 publications

References 38 publications

Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels

Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

A Novel Role of Exogenous Carbon Monoxide on Protecting Cardiac Function and Improving Survival against Sepsis via Mitochondrial Energetic Metabolism Pathway

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