Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster

Kim, Ji Eun; Bauer, Miranda M.; Mendoza, Kristelle M.; Reed, Kent M.; Coulombe, Roger A.

doi:10.1016/j.gene.2009.11.001

Cited by 19 publications

(13 citation statements)

References 55 publications

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“…In all cases the GSTA sequences of wild and heritage birds clustered with their domestic turkey homologs, confirming amplification of the target loci. On average, amino acid sequences of GSTAs from turkeys and chicken orthologues were 95% similar with the exception of chicken GSTA1 (cGSTA1) and domestic turkey tGSTA1.2 (81%), tGSTA1.3 (82%) [20], [21]. Clustering of the turkey and chicken sequences reflects the duplication of GSTA s prior to divergence of the two avian species.…”

Section: Resultsmentioning

confidence: 97%

“…Two domains consist of a thioredoxin-like N-terminal domain and a helical C-terminal domain. Like domestic breeds [20], all GSTAs from wild and heritage turkeys possess ten α-helices and five β-strands; N-terminal domain contains α1-β3/β1–4 and C-terminus contains α4-α10/β5. These alignments showed that all GSTAs possess four alpha-class signature motifs, except that GSTA1.1 lacked one motif (PVxEKVLKxHGxxxL) in residues 134–148 of the C-terminal domain, which did not appear to have a discernible effect on the catalytic activities of this form toward GST substrates (Table 4).…”

Section: Resultsmentioning

confidence: 99%

“…Putative amino acid sequences of all GSTAs were aligned using ClustalW 2.0.12 (http://www.ebi.ac.uk/Tools/clustalw2/). Predictive secondary structures in wild and heritage turkey were compared with alpha-class GSTs of domestic turkey [20], [21] using PSIPRED Protein Structure Prediction Server software program (http://bioinf.cs.ucl.ac.uk/psipred/). …”

Section: Methodsmentioning

confidence: 99%

“…Domestic turkeys possess six alpha-class GST genes ( tGSTA s) the homologues to AFB 1 -protective GSTAs in mice and in other species [20], [21]. Unlike the hepatic forms of turkey GSTs, which show no detectable AFBO-trapping ability, all recombinant and heterologously-expressed tGSTAs possessed measurable and comparable AFBO-conjugating activity; further, there is no apparent correlation between individual amino acid residues and AFBO-conjugation activity among the tGSTAs [21].…”

Section: Introductionmentioning

confidence: 99%

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Alpha-Class Glutathione S-Transferases in Wild Turkeys (Meleagris gallopavo): Characterization and Role in Resistance to the Carcinogenic Mycotoxin Aflatoxin B1

et al. 2013

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Domestic turkeys (Meleagris gallopavo) are one of the most susceptible animals known to the toxic effects of the mycotoxin aflatoxin B1 (AFB1), a potent human hepatocarcinogen, and universal maize contaminant. We have demonstrated that such susceptibility is associated with the inability of hepatic glutathione S-transferases (GSTs) to detoxify the reactive electrophilic metabolite exo-AFB1-8,9-epoxide (AFBO). Unlike their domestic counterparts, wild turkeys, which are relatively AFB1-resistant, possess hepatic GST-mediated AFBO conjugating activity. Here, we characterized the molecular and functional properties of hepatic alpha-class GSTs (GSTAs) from wild and domestic turkeys to shed light on the differences in resistance between these closely related strains. Six alpha-class GST genes (GSTA) amplified from wild turkeys (Eastern and Rio Grande subspecies), heritage breed turkeys (Royal Palm) and modern domestic (Nicholas strain) turkeys were sequenced, and catalytic activities of heterologously-expressed recombinant enzymes determined. Alpha-class identity was affirmed by conserved GST domains and four signature motifs. All GSTAs contained single nucleotide polymorphisms (SNPs) in their coding regions: GSTA1.1 (5 SNPs), GSTA1.2 (7), GSTA1.3 (3), GSTA2 (3), GSTA3 (1) and GSTA4 (2). E. coli-expressed GSTAs possessed varying activities toward GST substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (ECA), cumene hydroperoxide (CHP). As predicted by their relative resistance, livers from domestic turkeys lacked detectable GST-mediated AFBO detoxification activity, whereas those from wild and heritage birds possessed this critical activity, suggesting that intensive breeding and selection resulted in loss of AFB1-protective alleles during domestication. Our observation that recombinant tGSTAs detoxify AFBO, whereas their hepatic forms do not, implies that the hepatic forms of these enzymes are down-regulated, silenced, or otherwise modified by one or more mechanisms. These data may inform of possible molecular mechanisms of resistance to AFB1, and may also have the benefit of identifying genetic markers which could be used to enhance AFB1 resistance in modern domestic strains.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alpha-Class Glutathione S-Transferases in Wild Turkeys (Meleagris gallopavo): Characterization and Role in Resistance to the Carcinogenic Mycotoxin Aflatoxin B1

et al. 2013

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“…Six tGSTA genes have been amplified, cloned and heterologously expressed turkey liver (GSTA1.1, GSTA1.2, GSTA1.3, GSTA2, GSTA3, and GSTA4) [90,91]. Hepatic cytosolic GST enzymes from domestic turkey have essentially no AFBO-conjugating activity [40,91].…”

Section: Sensitivity: Poultrymentioning

confidence: 99%

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

2015

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This review is a comprehensive introduction to the effects of poultry exposure to the toxic and carcinogenic mycotoxin aflatoxin B1 (AFB1). The relationship between AFB1 sensitivity and metabolism, major direct and indirect effects of AFB1, recent studies of gene expression and transcriptome responses to exposure, and mitigation strategies to reduce toxicity are discussed. Exposure to AFB1 primarily occurs by consumption of contaminated corn, grain or other feed components. Low levels of residual AFB1 in poultry feeds can cause reduction in growth, feed conversion, egg production, and compromised immune functions, resulting in significant economic costs to producers. Thus, AFB1 acts as a "force multiplier" synergizing the adverse effects of microbial pathogens and other agents, and factors detrimental to poultry health. Domestic turkeys (Meleagris gallopavo) are one of the most sensitive animals known to AFB1 due, in large part, to a combination of efficient hepatic bioactivation by cytochromes P450 1A5 and 3A37, and deficient hepatic glutathione-S-transferase (GST)-mediated detoxification. Because of their sensitivity, turkeys are a good model to investigate chemopreventive treatments and feed additives for their ability to reduce AFB1 toxicity. Transcriptome analysis (RNA-seq) of turkey poults (liver and spleen) has identified AFB1-induced gene expression changes in pathways of apoptosis, carcinogenesis, lipid regulation, antimicrobial activity, cytotoxicity and antigen presentation. Current research focuses on further identifying the molecular mechanisms OPEN ACCESSAgriculture 2015, 5 743 underlying AFB1 toxicity with the goal of reducing aflatoxicosis and improving poultry health.

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Heterologous expression and functional characterization of avian mu-class glutathione S-transferases

Bunderson

Kim

Croasdell

et al. 2013

Comparative Biochemistry and Physiology Part C: Toxicology &

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Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster

Cited by 19 publications

References 55 publications

Alpha-Class Glutathione S-Transferases in Wild Turkeys (Meleagris gallopavo): Characterization and Role in Resistance to the Carcinogenic Mycotoxin Aflatoxin B1

Alpha-Class Glutathione S-Transferases in Wild Turkeys (Meleagris gallopavo): Characterization and Role in Resistance to the Carcinogenic Mycotoxin Aflatoxin B1

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

Heterologous expression and functional characterization of avian mu-class glutathione S-transferases

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