Induction of Heme Oxygenase-1 Can Act Protectively against Cardiac Ischemia/Reperfusion in Vivo

Hangaishi, Misako; Ishizaka, Nobukazu; Aizawa, Toru; Kurihara, Yukiko; Taguchi, Junichi; Nagai, Ryozo; Kimura, Satoshi; Ohno, Minoru

doi:10.1006/bbrc.2000.3973

Cited by 113 publications

(78 citation statements)

References 22 publications

(17 reference statements)

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“…Indeed, considerable evidence suggests an important role for HO-1 in cytoprotection. The induction of HO-1 by chemical inducers or selective overexpression of HO-1 provides cellular protection in cultured cells and in several animal models of brain, heart, kidney, lung, and liver failure (Abraham et al, 1995;Agarwal et al, 1995;Amersi et al, 1999;Otterbein et al, 1999;Panahain et al, 1999;Clark et al, 2000;Hangiashi et al, 2000;Yet et al, 2001;Coito et al, 2002). Studies with HO-1 À/À mice also support the functional significance of HO-1 in cytoprotection.…”

Section: Ho-1 and Cell Deathmentioning

confidence: 95%

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Durante

2003

Journal Cellular Physiology

143

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Heme oxygenase-1 (HO-1) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO-1 originally centered on its heme-degrading function, recent findings indicate that HO-1 exerts other biologically important actions. Emerging evidence suggests that HO-1 plays a critical role in growth regulation. Deletion of the HO-1 gene or inhibition of HO-1 activity results in growth retardation and impaired fetal development, whereas HO-1 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO-1 are not well established, HO-1 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO-1 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO-1 are highly variable and may reflect a role for HO-1 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO-1 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO-1 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO-1 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders.

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Section: Ho-1 and Cell Deathmentioning

confidence: 95%

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Durante

2003

Journal Cellular Physiology

143

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“…7 Rats were anesthetized and artificially ventilated with a respirator (model 683; Harvard Apparatus). The proximal portion of the left anterior descending coronary artery was occluded with a suture.…”

Section: Ischemia-reperfusion Proceduresmentioning

confidence: 99%

“…4 HO-1 acts protectively against hypoxia 5,6 or ischemia-reperfusion injury. 7,8 Biliverdin, a byproduct of heme catabolism, is endogenously converted to bilirubin and protects tissues. 9 CO, another product of heme catabolism, is usually regarded as a toxic species that disrupts cellular respiration.…”

mentioning

confidence: 99%

“…The concentration of carboxyhemoglobin (HbCO) in blood was measured by a hemoximeter (model OSM3; Radiometer Trading Co), using 100 L of arterial blood. Other rats were randomized to receive 1 of the following treatments: intraperitoneal (IP) injection of 50 g zinc-protoporphyrin (ZnPP) (Funakoshi, Tokyo, Japan), a selective HO-1 inhibitor, 7 or vehicle (0.2 mL DMSO) twice, at 48 hours and at 24 hours before ischemia-reperfusion surgery, with or without pre-inhalation of 1000 ppm CO for 24 hours.…”

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confidence: 99%

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Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

Fujimoto

Ohno

Ayabe

et al. 2004

ATVB

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138

120

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Background-Carbon monoxide (CO) is postulated to protect tissues against several types of injuries. We investigated the role of CO in amelioration of cardiac ischemia-reperfusion injury in vivo and the mechanisms involved in it. Methods and Results-Rats inhaled CO (250 ppm, 500 ppm, or 1000 ppm) for 24 hours in a chamber after myocardial ischemia-reperfusion induced by occluding the left anterior descending coronary artery for 30 minutes. Pre-exposure to 1000 ppm of CO significantly reduced the ratio of infarct areas to risk areas and suppressed the migration of macrophages and monocytes into infarct areas, and the expression of tumor necrosis factor (TNF)-␣ in the heart; however, 250 ppm, 500 ppm of CO, or low barometric pressure hypoxia (0.5 atm) did not affect them. Exposure to 1000 ppm CO resulted in the activation of p38 mitogen-activated protein kinase (p38MAPK), protein kinase B␣(Akt), endothelial nitric oxide synthase (eNOS), and cyclic guanosine monophosphate (cGMP) in the myocardium. Inhibition of p38MAPK, PI3kinase, NO, and soluble guanylate cyclase with SB203580, wortmannin, N(G)-nitro-L-arginine methyl ester (L-NAME), and methylene blue, respectively, attenuated the cytoprotection by CO. Conclusion-CO has beneficial effects on cardiac ischemia-reperfusion injury; this effect is mediated by p38MAPK pathway and Akt-eNOS pathway, including production of cGMP.

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“…Like GLUT1, heme oxygenase-1 (HO-1) has been characterized as a hypoxia-inducible gene in cardiomyocyte cells (8). HO-1 is a stress-responsive protein that has recently been shown to ameliorate the damage sustained by the heart from an ischemia-reperfusion insult (9,10).…”

mentioning

confidence: 99%

Activation of the Prolyl Hydroxylase Oxygen-sensor Results in Induction of GLUT1, Heme Oxygenase-1, and Nitric-oxide Synthase Proteins and Confers Protection from Metabolic Inhibition to Cardiomyocytes

Wright

Higgin

Raines

et al. 2003

Journal of Biological Chemistry

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Recently an oxygen-sensing/transducing mechanism has been identified as a family of O 2 -dependent prolyl hydroxylase domain-containing enzymes (PHD). In normoxia, PHD hydroxylates a specific proline residue that directs the degradation of constitutively synthesized hypoxia-inducible factor-1␣. During hypoxia, the cessation of hydroxylation of this proline results in less degradation and thus increases hypoxia-inducible factor-1␣ protein levels. In this study we have examined the consequences of activating the PHD oxygen-sensing pathway in cultured neonatal myocytes using ethyl-3,4 dihydroxybenzoate and dimethyloxalylglycine, inhibitors that, similar to hypoxia, inhibit this family of O 2 -dependent PHD enzymes. Increased glucose uptake and enhanced glycolytic metabolism are classical cellular responses to hypoxia. Ethyl-3,4 dihydroxybenzoate treatment of cardiomyocyte cultures for 24 h increased [ 3 H]deoxy-4-glucose uptake concurrent with an induction of GLUT1 protein. In addition, ethyl-3,4 dihydroxybenzoate, dimethyloxalylglycine, and hypoxia treatments were found to induce protein levels of nitricoxide synthase-2 and heme oxygenase-1, two important cardioregulatory proteins whose expression in response to hypoxic conditions is poorly understood. In conjunction with these changes in gene expression, activation of the PHD oxygen-sensing mechanism was found to preserve myocyte viability in the face of metabolic inhibition with cyanide and 2-deoxyglucose. These results point to a key role for the PHD pathway in the phenotypic changes that are observed in a hypoxic myocyte and may suggest a strategy to pharmacologically induce protection in heart.

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Induction of Heme Oxygenase-1 Can Act Protectively against Cardiac Ischemia/Reperfusion in Vivo

Cited by 113 publications

References 22 publications

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

Activation of the Prolyl Hydroxylase Oxygen-sensor Results in Induction of GLUT1, Heme Oxygenase-1, and Nitric-oxide Synthase Proteins and Confers Protection from Metabolic Inhibition to Cardiomyocytes

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