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A review on hemeoxygenase-2: focus on cellular protection and oxygen response.

Muñoz-Sánchez J, Chánez-Cárdenas ME - Oxid Med Cell Longev (2014)

Bottom Line: Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function.HO-2 presents particular characteristics that made it a unique protein in the HO system.Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, 14269 Delegación Tlalpan, DF, Mexico.

ABSTRACT
Hemeoxygenase (HO) system is responsible for cellular heme degradation to biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date. Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue identity, share a similar fold and catalyze the same reaction. However, important differences between isoforms also exist. HO-1 isoform has been extensively studied mainly by its ability to respond to cellular stresses such as hemin, nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals, between others. On the contrary, due to its apparently constitutive nature, HO-2 has been less studied. Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function. HO-2 presents particular characteristics that made it a unique protein in the HO system. Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform. We summarize information on gene description, protein structure, and catalytic activity of HO-2 and particular facts such as its cellular impact and activity regulation. Finally, we call attention on the role of HO-2 in oxygen sensing, discussing proposed hypothesis on heme binding motifs and redox/thiol switches that participate in oxygen sensing as well as evidences of HO-2 response to hypoxia.

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Related in: MedlinePlus

Catalytic reaction of HOs and BVR. The sequence is shown in three stages, separated by three well-defined intermediates: ferric-hydroperoxide, α-meso-hydroxyheme, and α-verdoheme. The final products of the reaction are CO, biliverdin IXα, and Fe2+. Biliverdin IXα is then reduced by BVR.
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fig2: Catalytic reaction of HOs and BVR. The sequence is shown in three stages, separated by three well-defined intermediates: ferric-hydroperoxide, α-meso-hydroxyheme, and α-verdoheme. The final products of the reaction are CO, biliverdin IXα, and Fe2+. Biliverdin IXα is then reduced by BVR.

Mentions: Reaction starts with the formation of the ferric heme-HO complex. Ferric heme-iron is then reduced to a ferrous state by the first electron donated from NADPH by NADPH cytochrome P450 reductase. Molecular oxygen binds to the complex to form a metastable oxy-form and iron-bound oxygen is converted to a hydroperoxide intermediate (Fe3+-OOH), by receiving another electron from the NADPH cytochrome P450 reductase and a proton from the distal pocket water. Terminal oxygen of Fe3+-OOH attacks the α-meso-carbon of the porphyrin ring to form ferric α-meso-hydroxyheme. This species of heme reacts with molecular oxygen and yields the ferrous verdoheme-HO complex and CO. The oxy-verdoheme-HO complex is converted to ferric iron-biliverdin chelate via a hydroperoxide intermediate, which is still bound to HO protein. The iron of the ferric biliverdin is reduced to the ferrous state by the reductase in order to liberate Fe2+ and BV to complete the total HO reaction (Figure 2). In the in vitro reaction, the release of BV from the enzyme is the rate limiting step [35–37].


A review on hemeoxygenase-2: focus on cellular protection and oxygen response.

Muñoz-Sánchez J, Chánez-Cárdenas ME - Oxid Med Cell Longev (2014)

Catalytic reaction of HOs and BVR. The sequence is shown in three stages, separated by three well-defined intermediates: ferric-hydroperoxide, α-meso-hydroxyheme, and α-verdoheme. The final products of the reaction are CO, biliverdin IXα, and Fe2+. Biliverdin IXα is then reduced by BVR.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127239&req=5

fig2: Catalytic reaction of HOs and BVR. The sequence is shown in three stages, separated by three well-defined intermediates: ferric-hydroperoxide, α-meso-hydroxyheme, and α-verdoheme. The final products of the reaction are CO, biliverdin IXα, and Fe2+. Biliverdin IXα is then reduced by BVR.
Mentions: Reaction starts with the formation of the ferric heme-HO complex. Ferric heme-iron is then reduced to a ferrous state by the first electron donated from NADPH by NADPH cytochrome P450 reductase. Molecular oxygen binds to the complex to form a metastable oxy-form and iron-bound oxygen is converted to a hydroperoxide intermediate (Fe3+-OOH), by receiving another electron from the NADPH cytochrome P450 reductase and a proton from the distal pocket water. Terminal oxygen of Fe3+-OOH attacks the α-meso-carbon of the porphyrin ring to form ferric α-meso-hydroxyheme. This species of heme reacts with molecular oxygen and yields the ferrous verdoheme-HO complex and CO. The oxy-verdoheme-HO complex is converted to ferric iron-biliverdin chelate via a hydroperoxide intermediate, which is still bound to HO protein. The iron of the ferric biliverdin is reduced to the ferrous state by the reductase in order to liberate Fe2+ and BV to complete the total HO reaction (Figure 2). In the in vitro reaction, the release of BV from the enzyme is the rate limiting step [35–37].

Bottom Line: Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function.HO-2 presents particular characteristics that made it a unique protein in the HO system.Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, 14269 Delegación Tlalpan, DF, Mexico.

ABSTRACT
Hemeoxygenase (HO) system is responsible for cellular heme degradation to biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date. Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue identity, share a similar fold and catalyze the same reaction. However, important differences between isoforms also exist. HO-1 isoform has been extensively studied mainly by its ability to respond to cellular stresses such as hemin, nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals, between others. On the contrary, due to its apparently constitutive nature, HO-2 has been less studied. Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function. HO-2 presents particular characteristics that made it a unique protein in the HO system. Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform. We summarize information on gene description, protein structure, and catalytic activity of HO-2 and particular facts such as its cellular impact and activity regulation. Finally, we call attention on the role of HO-2 in oxygen sensing, discussing proposed hypothesis on heme binding motifs and redox/thiol switches that participate in oxygen sensing as well as evidences of HO-2 response to hypoxia.

Show MeSH
Related in: MedlinePlus