Disease relevance of AOX1

• Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosis [1].
• Free fatty acids and leptin, that are elevated in obesity, failed to upregulate AOX1 in vitro [2].
• Obesity is associated with low adiponectin, reduced hepatic PPAR-alpha activity and fatty liver, and AOX1 was found induced in the liver of rats on a high-fat diet when compared to controls [2].
• For example, pIB4 is an Escherichia coli - P. pastoris shuttle vector that also uses the AOX1 promoter to allow intracellular expression of endogenous and foreign genes in the latter organism [3].
• Tissue factor was expressed with a human influenza hemagglutinin tag fused at the C-terminus under control of the regulatory sequences from the Pichia AOX1 gene [4].

Psychiatry related information on AOX1

• This study presents data showing individual differences in aldehyde oxidase activity in human and monkey liver cytosols [5].

High impact information on AOX1

• Anaerobic reduction kinetics of the zucchini squash ascorbate oxidase (AO; L-ascorbate:oxygen oxidoreductase, EC 1.10.3.3) by pulse radiolytically produced CO2- radical ions were investigated [6].
• On the basis of these results, it was apparent that the success of 6- deoxyacyclovir as a prodrug in vivo would depend upon how well its desired activation by xanthine oxidase competed with the nonactivating oxidations by aldehyde oxidase [7].
• 6- Deoxyacyclovir and the major products of its oxidation by aldehyde oxidase lacked appreciable activity against herpes simplex type I in vitro [7].
• It was also oxidized by aldehyde oxidase (EC 1.2.3.1) largely to 8-hydroxy-6- deoxyacyclovir [2-amino-8-hydroxy-9-[(2-hydroxyethoxy)methyl]-9H-purine] and then to 8- hydroxyacyclovir [2-amino-6,8-dihydroxy-9[(2-hydroxyethoxy)methyl]-9H-purine] [7].
• The apoplastic enzyme ascorbate oxidase (AO) also regulates the reduction/oxidation (redox) state of the apoplastic ascorbate pool [8].

Chemical compound and disease context of AOX1

• The molybdenum iron-sulphur protein from Desulfovibrio gigas as a form of aldehyde oxidase [9].
• The intramolecular electron transfer (ET) between the type 1 Cu(I) and the type 2 Cu(II) sites of Alcaligenes xylosoxidans dissimilatory nitrite reductase (AxNiR) has been studied in order to compare it with the analogous process taking place in ascorbate oxidase (AO) [10].
• Pargyline protected human lymphoma U937 cells against UVB-induced apoptosis, by reducing AO activity, mitochondrial uncoupling and cytochrome c release [11].
• In order to establish an efficient process to decompose environmentally toxic aldehydes, dioxygen-dependent aldehyde oxidase (ALOD) from microorganisms was first sought, and some bacteria and actinomycetes were found to produce the enzyme in their cells [12].

Biological context of AOX1

• A sequence homologous to AOX2-UAS was also found in the AOX1 promoter, and in methanol-regulated promoters in other methylotrophic yeast [13].
• The C. neoformans alternative oxidase gene (AOX1) was found to exist as a single copy in the genome, and it encodes a putative protein of 401 amino acids [14].
• Different expression plasmids were constructed in which the cDNAs of the two receptors were cloned under the transcriptional control of the highly inducible promoter of the P. pastoris alcohol oxidase 1 (AOX1) gene [15].
• Strains using either the AOX1 or the GAP promoter were compared at different gene copy numbers [16].
• P. pastoris with a MutS phenotype was selected to express A33scFv, which was cloned under regulation of the methanol-inducible AOX1 promoter [17].

Anatomical context of AOX1

• The AO gene is highly expressed in glial cells of human spinal cord [1].
• The aox1 mutant strain was significantly less virulent than both the wild type and the reconstituted strain in the murine inhalational model, and it also had significantly impaired growth within a macrophage-like cell line [14].
• Incubation of O6-benzylguanine with human liver cytosol resulted in the formation of O6-benzyl-8-oxoguanine, which was inhibited by menadione, a potent inhibitor of aldehyde oxidase [18].
• Respiratory rates involving the alternative oxidase (AO) were studied in mitochondria from Tapesia acuformis [19].
• An oxidized product formed by cytosolic aldehyde oxidase was the predominant species both in urine and human hepatocytes in vitro [20].

Associations of AOX1 with chemical compounds

• The variation in AO activity among the various human livers was greater for NMN oxidase (> 40 fold) than for 6-methylpurine and benzaldehyde oxidase (< or = 3.6 fold) activity [21].
• The S-9 fractions were characterized for cytosolic aldehyde oxidase (AO) activity, using three different substrates [N1-methylnicotinamide (NMN), benzaldehyde and 6-methylpurine] [21].
• We also included discovery of polymorphic forms of genes that code for enzymes that are inhibited by tungsten: xanthine dehydrogenase, sulfite oxidase (SUOXgene), and aldehyde oxidase [22].
• Amphotericin B produced changes in the expression of genes involved in small-molecule transport (ENA21), and in cell stress (YHB1, CTA1, AOX1, and SOD2) [23].
• This recombinant protein C activator was expressed in Pichia pastoris as a secreted glycoprotein (ILPCA) using the AOX1 promoter and the alpha-factor signal sequence [24].

Regulatory relationships of AOX1

• Recombinant human Reg IV was efficiently expressed under the control of the AOX1 gene promoter in Pichia pastoris using the MutS strain KM71H [25].
• Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro [2].

Other interactions of AOX1

• Two 2039 bp koala liver AOX cDNAs, designated AOX1 and AOX2, were cloned by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends [26].
• The human molybdenum cofactor sulfurase (HMCS) gene, the human ma-l homologue, is therefore a candidate gene responsible for classical xanthinuria type II, which involves both XDH and AO deficiencies [27].
• The human endothelin B receptor (ET(B) receptor) was produced in the methylotrophic yeast Pichia pastoris under transcriptional control of the highly inducible alcohol oxidase 1 (AOX1) gene promoter [28].
• Xanthine dehydrogenase and aldehyde oxidase, but not sulfite oxidase and nitrate reductase, require the post-translational sulfuration of their Mo-site for becoming active [29].
• However, one would expect interindividual variation in the extent of oxidation of O6-benzylguanine depending on the levels of aldehyde oxidase, CYP1A2, and CYP3A4 [18].

Analytical, diagnostic and therapeutic context of AOX1

• GeneChip experiments indicated that recombinant adiponectin downregulates aldehyde oxidase 1 (AOX1) expression and this was confirmed by real-time RT-PCR and immunoblot [2].
• METHODS: Amplifying hVEGF165 cDNA by PCR, after confirmed by DNA sequence analysis, the gene was inserted into the Pichia pastoris expression vector pPIC9K containing AOX1 promoter and a secreting signal peptides, the recombinant expression plasmid pPIC9K/VEGF165 was constructed and transformed into KM71 [30].
• Significant correlations were found between AO activity and various growth indices (age, body weight, body surface area, and liver volume) [31].
• This work focuses on the elucidation of the electron-transfer mechanism of the monoenzymatic unmediated AO-modified biosensor [32].
• Southern blot analysis conducted on genomic DNA from various animal species with specific cDNA probes indicates that the AO gene is less conserved than the XOR gene during evolution [33].

References