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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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Comparison between HO-1 and HO-2 primary structures. Figure based on information reported by [66–68].
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fig4: Comparison between HO-1 and HO-2 primary structures. Figure based on information reported by [66–68].

Mentions: Crystallographic studies of HOs revealed that proteins are mostly α-helical with short loop segments that connect adjoining helices. In general, the secondary structure of HO-2 closely resembles apo- and heme-bound HO-1 [67, 83]. Primary sequence alignment shows that HO-1 and HO-2 exhibit two regions of sequence divergence: one is around residue 127 and the other is near the C-terminal between 240 and 295 (HO-2 numbering) (Figure 4) [66, 69]. Evidences show that differences in C-terminal of HO-1 and HO-2 play regulatory roles. It has been reported that HO-1 undergoes a regulated intramembranal proteolysis of 52 amino acids at C-terminal in order to be translocated to the nucleus and it has been hypothesized that HO-1 alters binding of transcription factors that respond to hypoxic or oxidative stress conditions affecting gene expression [84]. This proteolysis and nuclear translocation occurs in hypoxic conditions and is a specific behavior of HO-1 [85]. On the other hand, HO-2 in its C-terminal region contains particular sequences between residues 255 and 287 named the heme regulatory motifs (HRMs) (see below).


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

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

Comparison between HO-1 and HO-2 primary structures. Figure based on information reported by [66–68].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Comparison between HO-1 and HO-2 primary structures. Figure based on information reported by [66–68].
Mentions: Crystallographic studies of HOs revealed that proteins are mostly α-helical with short loop segments that connect adjoining helices. In general, the secondary structure of HO-2 closely resembles apo- and heme-bound HO-1 [67, 83]. Primary sequence alignment shows that HO-1 and HO-2 exhibit two regions of sequence divergence: one is around residue 127 and the other is near the C-terminal between 240 and 295 (HO-2 numbering) (Figure 4) [66, 69]. Evidences show that differences in C-terminal of HO-1 and HO-2 play regulatory roles. It has been reported that HO-1 undergoes a regulated intramembranal proteolysis of 52 amino acids at C-terminal in order to be translocated to the nucleus and it has been hypothesized that HO-1 alters binding of transcription factors that respond to hypoxic or oxidative stress conditions affecting gene expression [84]. This proteolysis and nuclear translocation occurs in hypoxic conditions and is a specific behavior of HO-1 [85]. On the other hand, HO-2 in its C-terminal region contains particular sequences between residues 255 and 287 named the heme regulatory motifs (HRMs) (see below).

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