Disease relevance of AKR7A2

• Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease [1].
• Overall, 73 (19.7%) were HIV-1 positive, but prevalence was three times higher among the 237 women of Amhara ethnicity compared to the 112 of Afar ethnicity (24.9% vs 8.0%, p < 0.001), and almost three times higher for urban compared to rural residents (23.2% vs 8.8%, p < 0.001) [2].
• There was a significant difference in the prevalence of brucellosis (chi2 = 7.91, p < 0.05), which was highest in Afar (5.2%) followed by Somali (2.8%) and Borena (1.2%) regions [3].
• Mastitis in lactating camels (Camelus dromedarius) in Afar Region, north-eastern Ethiopia [4].
• Haematobium schistosomiasis among seminomadic and agricultural Afar in Ethiopia [5].

High impact information on AKR7A2

• Resolution of these problems would shed light on hominid phylogeny in general and on the ancestry of later Australopithecus and Homo. Fossils discovered in the Afar of Ethiopia in 1990 constitute the first major addition to the 3-4 million year (Myr) hominid record since the 1970s [6].
• From this region we have now cloned a gene encoding a protein of 330 amino acids that is 78% identical with the Rattus norvegicus aflatoxin B1 aldehyde reductase (Afar) and, therefore, likely represents its human homologue [7].
• In rat liver, Afar is strongly inducible by the antioxidants ethoxyquin and butylated hydroxyanisole, which protect the rat against aflatoxin B1-induced liver tumorigenesis by detoxifying its genotoxic and cytotoxic dialdehyde [7].
• Fluorescent in situ hybridization localized AFAR1 to rat chromosome 5q36.5, a region that is syntenic with human chromosome 1p35-1p36.1 where AKR7A2 resides [8].
• The 5'-flanking region of AFAR1 was isolated by polymerase chain reaction-based genome walking, and resulted in the isolation of approximately 900 bp of genomic DNA upstream from the TSS [8].

Chemical compound and disease context of AKR7A2

• Reliable estimation of HIV-1 prevalence in Afar Region will require more flexible strategies that permit sampling of rural Afar residents [2].

Biological context of AKR7A2

• Also, AKR7A2 was found to exhibit a narrow substrate specificity, with activity being restricted to succinic semialdehyde (SSA), 2-nitrobenzaldehyde, pyridine-2-aldehyde, isatin, 1,2-naphthoquinone (1,2-NQ) and 9,10-phenanthrenequinone [9].
• The deduced amino acid sequence of AKR7A3 shares 80 and 88% identity with rat AKR7A1 and human AKR7A2, respectively [10].
• This novel human aldo-keto reductase (AKR) has been cloned from a liver cDNA library, and together with the rat protein, establishes the AKR7 family of the AKR superfamily [11].
• Characterization of these clones has shown that rat AFAR1 is approximately 8 kb long and comprises seven exons and six introns [8].
• Use of a gene expression reporter assay demonstrated that this cloned 5'-flanking region of AFAR1 could support transcription in the rat liver 34 (RL34) epithelial cell line [8].

Anatomical context of AKR7A2

• Western blotting of extracts from brain, heart, kidney, liver, lung, prostate, skeletal muscle, small intestine, spleen and testis showed that AKR7A2 is present in all of the organs examined, and AKR1B1 is similarly widely distributed in human tissues [9].
• Furthermore, total AKR7A2 protein levels were elevated in the cerebral cortex of patients with AD versus control individuals [1].
• In the midbrain, AKR7A2 was found in glia and neuromelanin-containing neurons of the substantia nigra, and the periaqueductal gray [1].
• Our results show that in the cerebral cortex and hippocampus, AKR7A2 is primarily localized to glial cells, astrocytes and microglia [1].

Associations of AKR7A2 with chemical compounds

• Aflatoxin B1 aldehyde reductases, specifically the NADPH-dependent aldo-keto reductases of rat (AKR7A1) and human (AKR7A2), are known to metabolize the AFB1 dihydrodiol by forming AFB1 dialcohol [10].
• Comparison between the kinetic properties of AKR7A2 and AKR1A1 showed that both recombinant enzymes exhibited roughly similar k(cat)/K(m) values for SSA, 1,2-NQ and 16-ketoestrone [9].
• In the present study, we examined the cellular expression of AKR family member, succinic semialdehyde reductase (AKR7A2) that reduces toxic aldehydes as well as catalyzing the biosynthesis of the neuromodulator gamma-hydroxybutyrate (GHB) [1].
• Although the two AKR7 proteins are predicted to possess distinct secondary structural features which distinguish them from the prototypic AKR1 family of AKRs, the catalytic- and NADPH-binding residues appear to be conserved in both families [11].
• Both BHA and BHT were also able to induce this enzyme but, by contrast, PB was found to be a poor inducer of AFB1-AR [12].

Analytical, diagnostic and therapeutic context of AKR7A2

• Immunohistochemistry of human kidney demonstrated that AKR7A2 is expressed in a similar fashion to the AKR1 family members in proximal and distal convoluted renal tubules [9].
• Molecular cloning, expression and catalytic activity of a human AKR7 member of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1-aldehyde reductase [11].
• Here we report on stratigraphically associated Late Middle Pleistocene artefacts and fossils from fluvial and lake margin sandstones of the Upper Herto Member of the Bouri Formation, Middle Awash, Afar Rift, Ethiopia [13].
• HIV-1 seroprevalence and subtypes in police recruits from Afar regional state, Ethiopia [14].
• According to the Demographic and Health Survey (DHS) 2000, only 4.5% of the population of Afar Region is of Amhara ethnicity, and 7.8% urban residents [2].

References