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

Bunderson, Brett R.; Kim, Ji Eun; Croasdell, Amanda; Mendoza, Kristelle M.; Reed, Kent M.; Coulombe, Roger A.

doi:10.1016/j.cbpc.2013.05.007

Cited by 9 publications

(5 citation statements)

References 45 publications

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“…In most animals, AFBO is detoxified primarily by hepatic glutathione S-transferases (GSTs) [3]. The most likely mechanism for the extreme susceptibility in domesticated turkeys is dysfunctional hepatic GSTs rendering them unable to detoxify AFB 1 [10,11,12,13,14]. In this regard, domesticated turkeys closely resemble humans in that they also lack hepatic alpha-class GSTs (GSTA) with high activity toward AFB 1 (seen in mice and rats) suggesting that turkeys may represent a better model to study aflatoxin toxicology than either of these rodent species [9].…”

Section: Introductionmentioning

confidence: 99%

Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys

Reed

Mendoza

Coulombe

2019

Toxins

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The nearly-ubiquitous food and feed-borne mycotoxin aflatoxin B1 (AFB1) is carcinogenic and mutagenic, posing a food safety threat to humans and animals. One of the most susceptible animal species known and thus a good model for characterizing toxicological pathways, is the domesticated turkey (DT), a condition likely due, at least in part, to deficient hepatic AFB1-detoxifying alpha-class glutathione S-transferases (GSTAs). Conversely, wild turkeys (Eastern wild, EW) are relatively resistant to the hepatotoxic, hepatocarcinogenic and immunosuppressive effects of AFB1 owing to functional gene expression and presence of functional hepatic GSTAs. This study was designed to compare the responses in gene expression in the gastrointestinal tract between DT (susceptible phenotype) and EW (resistant phenotype) following dietary AFB1 challenge (320 ppb for 14 days); specifically in cecal tonsil which functions in both nutrient absorption and gut immunity. RNAseq and gene expression analysis revealed significant differential gene expression in AFB1-treated animals compared to control-fed domestic and wild birds and in within-treatment comparisons between bird types. Significantly upregulated expression of the primary hepatic AFB1-activating P450 (CYP1A5) as well as transcriptional changes in tight junction proteins were observed in AFB1-treated birds. Numerous pro-inflammatory cytokines, TGF-β and EGF were significantly down regulated by AFB1 treatment in DT birds and pathway analysis suggested suppression of enteroendocrine cells. Conversely, AFB1 treatment modified significantly fewer unique genes in EW birds; among these were genes involved in lipid synthesis and metabolism and immune response. This is the first investigation of the effects of AFB1 on the turkey gastro-intestinal tract. Results suggest that in addition to the hepatic transcriptome, animal resistance to this mycotoxin occurs in organ systems outside the liver, specifically as a refractory gastrointestinal tract.

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Section: Introductionmentioning

confidence: 99%

Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys

Reed

Mendoza

Coulombe

2019

Toxins

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“…Like wild strains, the Royal Palm turkey, a heritage breed, retains hepatic and in vitro activity [99]. tGSTM enzymes were also amplified, cloned and heterologously expressed from the livers of wild and domestic turkeys, but had no measurable affinity toward AFBO, and therefore are not thought to be involved in AFB1 detoxification [100].…”

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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“…Interestingly, it was reported that Asian population were more vulnerable to viral hepatic cirrhosis [ 29 ]. The popularity of GSTM1 null has been reported to vary with different ethnic populations, 30% of Caucasians while 70% of Asians [ 14 ]. The high prevalence of GSTM1 null among Asians may lead to the increased vulnerability to HC.…”

Section: Discussionmentioning

confidence: 99%

“…The major GSTs family isoforms can be categorized into α (alpha), μ (mu), θ (theta), and ∏ (pi) classes [ 13 ]. Glutathione S -transferase mu (GSTM1) is one of the most widely expressed gene [ 14 ]. Null genotype was reported to be the most common variant of GSTM1 among populations [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

The influence of polymorphic GSTM1 gene on the increased susceptibility of non-viral hepatic cirrhosis: evidence from observational studies

Zhao

et al. 2018

Eur J Med Res

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It is reported that glutathione S-transferase mu (GSTM1) polymorphism is associated with non-viral hepatic cirrhosis (HC). However, some studies showed different views. Therefore, in this paper, a meta-analysis was conducted to get a more comprehensive understanding of GSTM1 polymorphisms in non-viral HC susceptibility. The results showed that GSTM1 null was associated with the increased risk of non-viral HC (OR = 1.337, 95% CI 1.112–1.804, p = 0.005). Subgroup analysis of cirrhosis type revealed that GSTM1 null was a prominent risk factor for alcoholic HC (OR = 1.416, 95% CI 1.112–1.804, p = 0.005). Meanwhile, subgroup analysis of population indicated that the significant differences only existed in Asian population (OR = 1.719, 95% CI 1.212–2.438, p = 0.002). In hospital-based studies, patients with GSTM1 null were more likely in risk of HC (OR = 1.426, 95% CI 1.092–1.863, p = 0.009). Subgroup analysis using genotyping method showed a significant association between GSTM1 null genotype and HC occurrence in the studies employing the multiple PCR genotyping method (OR = 1.559, 95% CI 1.171–2.076, p = 0.002). Based on the results of this analysis, it was concluded that GSTM1 null genotype could increase the susceptibility of non-viral hepatic cirrhosis. In addition, alcohol intake, Asian ethnicity, sample source from hospital and multiple PCR genotyping method may also influence the susceptibility of hepatic cirrhosis.

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

Cited by 9 publications

References 45 publications

Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys

Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys

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

The influence of polymorphic GSTM1 gene on the increased susceptibility of non-viral hepatic cirrhosis: evidence from observational studies

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