Disease relevance of oxooxonium

• By decreasing HO2 activity, one would expect more neuronal damage after oxidative stress injury with possible direct implications to acute and chronic neurodegenerative disorders [1].
• The production of singlet oxygen (1O2) and superoxide radicals (O(2) or HO2), the formation of interstrand cross-links (ICL) in DNA, and the skin photosensitization reaction caused by CCT or the ingredients present in tar preparations have been examined [2].
• Identification of four phage resistance plasmids from Lactococcus lactis subsp. cremoris HO2 [3].
• In intact mice, we show an increased incidence of apoptotic morphology in the penumbra area surrounding the infarct core in HO2(-/-) mice undergoing transient focal ischemia [4].
• Bilirubin itself in nanomolar concentrations is neuroprotective, while HO2 deletion (HO2(-/-)) leads to increased neurotoxicity in brain cultures and increased neural damage following transient cerebral ischemia in intact mice [4].

High impact information on oxooxonium

• In the nervous system CO is formed by a subtype of heme oxygenase (HO) designated HO2 [5].
• Defects in myenteric plexus neurotransmission occur both in mice with targeted deletion of genes for HO2 and neuronal NOS [5].
• The majority of ganglia in the myenteric plexus possess both HO2 and neuronal NO synthase (NOS) [5].
• HO2 also occurs in other autonomic ganglia including the petrosal, superior cervical and nodose ganglia [5].
• The neuronal form of HO, HO2, is also cytoprotective [6].

Biological context of oxooxonium

• Perhydroxyl radical (HOO.) initiated lipid peroxidation. The role of fatty acid hydroperoxides [7].
• An inverse kinetic isotope effect upon the enzymatic reduction of O2*- is also observed and proposed to arise from rate-determining proton transfer which leads to the formation of HO2* in the SOD active site [8].
• Under the latter conditions, more superoxide was protonated and uncharged (HO2*), and the penetrance of superoxide was proportional to the concentration of this species [9].
• More recent analysis of HO2 suggested that it also plays a role in phy assembly and photomorphogenesis but the ho2 mutant phenotype is more subtle than that of hy1 mutants [10].
• However, in acetonitrile this termination process is accompanied by termination via the cross-reaction of the terpinenyl radical, T*, with the HOO* radical under conditions of relatively high [TH] (140-1000 mM) and low [O(2)] (2.0-5.5 mM) [11].

Anatomical context of oxooxonium

• Carbon monoxide, formed from HO2, is a putative neurotransmitter in the brain and peripheral autonomic nervous system [4].
• We now show that neural damage following middle cerebral artery occlusion (MCAO) and reperfusion, a model of focal ischemia of vascular stroke, is substantially worsened in HO2(-/-) animals [12].
• Superoxide (HO2) generation was measured in either an aliquot of white blood cells (WBCs) recovered from bronchoalveolar lavage (BAL) or from blood [13].
• Due to two possible catalytic cycles, peroxidative and hydroxylic, peroxidases can generate reactive oxygen species (ROS) (*OH, HOO*), polymerise cell wall compounds, and regulate H2O2 levels [14].
• METHODS: Total RNA was extracted from MCP-1 treated macrophage line U937 and normal U937 cells, reversely transcribed to cDNA, and then screened in parallel with HO2 human cDNA array chip [15].

Associations of oxooxonium with other chemical compounds

• Chem. Soc. 103, 7020-7025) demonstrated that HOO., generated by pulse radiolysis, initiates peroxidation in ethanol/water fatty acid dispersions by abstraction of the bis-allylic hydrogen atom from a polyunsaturated fatty acid [7].
• The neutral side chain of the distal histidine (His64) inhibits autooxidation by hydrogen bonding to bound oxygen, preventing both HO2 dissociation and the oxidative bimolecular reaction with deoxymyoglobin [16].
• Phenotypic analysis of a T-DNA insertion mutant of Arabidopsis HO2 revealed that the second HO subfamily also contributes to phytochromobilin synthesis [17].
• In neutral solutions, desferrioxamine (Desferal) can react with the superoxide free radical, O2.- (possibly through its protonated form HO2.), to form a relatively stable nitroxide free radical, which can have a half-life of approx. 10 min at room temperature [18].
• The kinetics of the FeCl(3)-inhibited autoxidation are consistent with chain-termination via the following: Fe(3+) + HOO. <==>[Fe(IV)-OOH](3+) and [Fe(IV)-OOH](3+) + HOO. --> Fe(3+) + H2O2 + O2 [19].

Gene context of oxooxonium

• Two HO active isozymes exist: HO1, an inducible heat shock protein, and HO2, which is constitutive and highly concentrated in neurons [20].
• Through a phenotypic analysis of T-DNA insertion mutants affecting HO3 and HO4 in combination with mutants affecting HY1 or HO2, we demonstrate that both of the encoded proteins also have roles in photomorphogenesis, especially in the absence of HY1 [10].
• Hepatic expression of HO2 (a constitutive isoform of HO) was unaffected by sex or trauma and hemorrhage [21].
• The patterns of Arabidopsis HO1 and HO2 expression suggest that the products of both genes overlap temporally and spatially [17].
• The constitutive forms of the enzyme are differentially activated, with calcium entry stimulating NOS by binding to calmodulin, whereas calcium entry activates protein kinase C to phosphorylate and activate HO2 [6].

Analytical, diagnostic and therapeutic context of oxooxonium

• Near-infrared spectroscopy was used to monitor HO2 formed by pulsed laser photolysis of Cl2-O2-CH3OH-N2 mixtures [22].

References