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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

Physiological roles of HO-2 enzymatic activity products. Heme is cleaved by HO-2 producing equimolar amounts of CO, Fe2+, and BV. Enzymatic reaction requires NADPH, Cyt P450, and O2. CO has antiapoptotic, antiproliferative, and anti-inflammatory activities through p38/MAPK processes. CO also regulates vascular tone via cGC/cGMP, stabilization of HIF-1α and inhibits NADPH oxidase and NOS. BV is metabolized to BR by NAD(P)H : BVR. Fe2+ is sequestered by ferritin but also can form DNIC, a complex with protective effects through inhibition of caspases activity. BVR: biliverdin reductase; cGC: guanylate cyclase; DNIC: iron-sulfur cluster dinitrosyl iron-sulfur complex; HIF-1α: alfa subunit of Hypoxia inducible factor-1; NO: nitric oxide; and NOS; nitric oxide synthase.
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fig1: Physiological roles of HO-2 enzymatic activity products. Heme is cleaved by HO-2 producing equimolar amounts of CO, Fe2+, and BV. Enzymatic reaction requires NADPH, Cyt P450, and O2. CO has antiapoptotic, antiproliferative, and anti-inflammatory activities through p38/MAPK processes. CO also regulates vascular tone via cGC/cGMP, stabilization of HIF-1α and inhibits NADPH oxidase and NOS. BV is metabolized to BR by NAD(P)H : BVR. Fe2+ is sequestered by ferritin but also can form DNIC, a complex with protective effects through inhibition of caspases activity. BVR: biliverdin reductase; cGC: guanylate cyclase; DNIC: iron-sulfur cluster dinitrosyl iron-sulfur complex; HIF-1α: alfa subunit of Hypoxia inducible factor-1; NO: nitric oxide; and NOS; nitric oxide synthase.

Mentions: The cytoprotective role of HO system comprises the reduction of cellular free heme and the generation of metabolites during the catalytic reaction. HO isoenzymes are positioned within endoplasmic reticulum, and in conjunction with NADPH cytochrome P450 reductase, split the tetrapyrrole heme ring to biliverdin (BV), free ferrous iron (Fe2+), and carbon monoxide (CO). BV is subsequently metabolized to bilirubin (BR) by Biliverdin Reductase (BVR) (Figure 1) [34].


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

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

Physiological roles of HO-2 enzymatic activity products. Heme is cleaved by HO-2 producing equimolar amounts of CO, Fe2+, and BV. Enzymatic reaction requires NADPH, Cyt P450, and O2. CO has antiapoptotic, antiproliferative, and anti-inflammatory activities through p38/MAPK processes. CO also regulates vascular tone via cGC/cGMP, stabilization of HIF-1α and inhibits NADPH oxidase and NOS. BV is metabolized to BR by NAD(P)H : BVR. Fe2+ is sequestered by ferritin but also can form DNIC, a complex with protective effects through inhibition of caspases activity. BVR: biliverdin reductase; cGC: guanylate cyclase; DNIC: iron-sulfur cluster dinitrosyl iron-sulfur complex; HIF-1α: alfa subunit of Hypoxia inducible factor-1; NO: nitric oxide; and NOS; nitric oxide synthase.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Physiological roles of HO-2 enzymatic activity products. Heme is cleaved by HO-2 producing equimolar amounts of CO, Fe2+, and BV. Enzymatic reaction requires NADPH, Cyt P450, and O2. CO has antiapoptotic, antiproliferative, and anti-inflammatory activities through p38/MAPK processes. CO also regulates vascular tone via cGC/cGMP, stabilization of HIF-1α and inhibits NADPH oxidase and NOS. BV is metabolized to BR by NAD(P)H : BVR. Fe2+ is sequestered by ferritin but also can form DNIC, a complex with protective effects through inhibition of caspases activity. BVR: biliverdin reductase; cGC: guanylate cyclase; DNIC: iron-sulfur cluster dinitrosyl iron-sulfur complex; HIF-1α: alfa subunit of Hypoxia inducible factor-1; NO: nitric oxide; and NOS; nitric oxide synthase.
Mentions: The cytoprotective role of HO system comprises the reduction of cellular free heme and the generation of metabolites during the catalytic reaction. HO isoenzymes are positioned within endoplasmic reticulum, and in conjunction with NADPH cytochrome P450 reductase, split the tetrapyrrole heme ring to biliverdin (BV), free ferrous iron (Fe2+), and carbon monoxide (CO). BV is subsequently metabolized to bilirubin (BR) by Biliverdin Reductase (BVR) (Figure 1) [34].

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