The catalytic activity of cytochrome P450 3A22 is critical for the metabolism of T-2 toxin in porcine reservoirs

Ge, Xiaohu; Wang, Junping; Liu, Jing; Jiang, Jun; Lin, Huina; Wu, Jun; Ouyang, Man; Tang, Xianqing; Zheng, Mingming; Liao, Ming; Deng, Yiqun

doi:10.1016/j.catcom.2010.08.003

Cited by 23 publications

(14 citation statements)

References 25 publications

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“…In pigs, after T-2 toxin exposure, the mRNA levels of CYP1A2 were not significantly induced, but those of CYP3A22 and CYP3A46 were markedly induced [10,11]. Furthermore, in vitro catalysis assays suggested that the two CYP3As could metabolize T-2 to form 3′OH-T-2.…”

Section: Resultsmentioning

confidence: 99%

“…Hepatocytes were isolated from the livers of 18-day-old chicken embryos by perfusion, and then, primary chicken embryonic hepatocytes were cultured [10]. After a 24 h growth period, the monolayer hepatocytes cultures were exposed to 0.1 μg/mL T-2 (dissolved in DMSO) or to an equal volume of DMSO used as a control.…”

Section: Methodsmentioning

confidence: 99%

“…In pigs, some CYP3As have been reported to transform T-2 into its hydroxylation products, but until now, the specific CYP subfamilies in chickens that transform T-2 toxin into its hydroxylation products have not been reported [10,11]. Herein, we investigated which cytochrome P450 isoforms in chicken were involved in T-2 metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Chicken Cytochrome P450 1A5 Is the Key Enzyme for Metabolizing T-2 Toxin to 3'OH-T-2

Shang

Jiang

Deng

2013

IJMS

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The transmission of T-2 toxin and its metabolites into the edible tissues of poultry has potential effects on human health. We report that T-2 toxin significantly induces CYP1A4 and CYP1A5 expression in chicken embryonic hepatocyte cells. The enzyme activity assays of CYP1A4 and CYP1A5 heterologously expressed in HeLa cells indicate that only CYP1A5 metabolizes T-2 to 3′OH-T-2 by the 3′-hydroxylation of isovaleryl groups. In vitro enzyme assays of recombinant CYP1A5 expressed in DH5α further confirm that CYP1A5 can convert T-2 into TC-1 (3′OH-T-2). Therefore, CYP1A5 is critical for the metabolism of trichothecene mycotoxin in chickens.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Chicken Cytochrome P450 1A5 Is the Key Enzyme for Metabolizing T-2 Toxin to 3'OH-T-2

Shang

Jiang

Deng

2013

IJMS

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“…The 0.05 g/ml T-2 dose was selected for microarray and 2-D DIGE analysis based on our previous 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay (29).…”

Section: Methodsmentioning

confidence: 99%

Integrated Transcriptional and Proteomic Analysis with In Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes

Wang

Jiang

Zhang

et al. 2011

Molecular & Cellular Proteomics

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Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of countermeasures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and

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“…T-2 toxin is known to induce apoptosis in mammalian cells; at the same time, there are relatively few notes about the topic on bird species [4,19]. Therefore, the aim of the investigation was to study the toxic effect of T-2 on chicken liver tissue using the antibodies p21 and p53 involved in apoptosis.…”

Section: Introductionmentioning

confidence: 99%

T-2 mycotoxin induced apoptosis in broiler’s liver tissue

Hussar

Järveots

Pendovski

et al. 2018

PoA

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Apoptosis is a process of programmed cell death that occurs in multicellular organisms. As T-2 toxin is known to induce apoptosis in mammalian cells, the aim of the present experiment was to study the toxic effect of T-2 on chicken liver tissue using apoptosis-related antibodies p21 and p53 which are involved in the p53/p21-mediated apoptotic signalling pathway.The experiment was conducted on fourteen 40-day-old broilers (Gallus gallus domesticus) who were divided into control and T-2 toxin groups. For the T-2 toxin group, T-2 toxin (Sigma, Germany) was dissolved in water and given per os for three consecutive days. The material of the liver was taken 24 hours after the last application. The specimens were fixed with 10% formalin and embedded into paraffin; slices 5 μm in thickness were cut followed by immunohistochemical staining with polyclonal primary antibodies p21 and p53 (Abcam, UK) according to the manufacturer's guidelines (IHC kit, Abcam, UK).Strong expression of p21 and p53 found in hepatocytes, endotheliocytes and around blood vessels together with large tissue destructions in T-2 toxin group birds' liver indicates apoptosis and histopathological changes in liver tissue during T-2 mycotoxicosis.

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The catalytic activity of cytochrome P450 3A22 is critical for the metabolism of T-2 toxin in porcine reservoirs

Cited by 23 publications

References 25 publications

Chicken Cytochrome P450 1A5 Is the Key Enzyme for Metabolizing T-2 Toxin to 3'OH-T-2

Chicken Cytochrome P450 1A5 Is the Key Enzyme for Metabolizing T-2 Toxin to 3'OH-T-2

Integrated Transcriptional and Proteomic Analysis with In Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes

T-2 mycotoxin induced apoptosis in broiler’s liver tissue

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