Structural-functional adaptations of porcine CYP1A1 to metabolize polychlorinated dibenzo-p-dioxins

Molcan, Tomasz; Świgońska, Sylwia; Orlowska, Karina; Myszczyński, Kamil; Nynca, Anna; Sadowska, Agnieszka; Ruszkowska, Monika; Jastrzebski, J; Ciereszko, Renata E.

doi:10.1016/j.chemosphere.2016.10.035

Cited by 11 publications

(15 citation statements)

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“…We also demonstrated that the TCDD binding to the porcine CYP1A1 active site resulted in a rapid closure of the enzyme substrate channels. This phenomenon may partially explain TCDD’s high resistance to biodegradation [ 59 ]. If the TCDD binding causes a continuous CYP1A1 blockage, the cellular response to TCDD may induce an extended synthesis of CYP1A1.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of long non-coding RNAs in porcine granulosa cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Ruszkowska

Nynca

Paukszto

et al. 2018

J Animal Sci Biotechnol

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BackgroundLong non-coding RNAs (lncRNAs) may regulate gene expression in numerous biological processes including cellular response to xenobiotics. The exposure of living organisms to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent environmental contaminant, results in reproductive defects in many species including pigs. The aims of the study were to identify and characterize lncRNAs in porcine granulosa cells as well as to examine the effects of TCDD on the lncRNA expression profile in the cells.ResultsOne thousand six hundred sixty-six lncRNAs were identified and characterized in porcine granulosa cells. The identified lncRNAs were found to be shorter than mRNAs. In addition, the number of exons was lower in lncRNAs than in mRNAs and their exons were longer. TCDD affected the expression of 22 lncRNAs (differentially expressed lncRNAs [DELs]; log2 fold change ≥ 1, P-adjusted < 0.05) in the examined cells. Potential functions of DELs were indirectly predicted via searching their target cis- and trans-regulated protein-coding genes. The co-expression analysis revealed that DELs may influence the expression of numerous genes, including those involved in cellular response to xenobiotics, dioxin metabolism, endoplasmic reticulum stress and cell proliferation. Aryl hydrocarbon receptor (AhR) and cytochrome P450 1A1 (CYP1A1) were found among the trans-regulated genes.ConclusionsThese findings indicate that the identified lncRNAs may constitute a part of the regulatory mechanism of TCDD action in granulosa cells. To our knowledge, this is the first study describing lncRNAs in porcine granulosa cells as well as TCDD effects on the lncRNA expression profile. These results may trigger new research directions leading to better understanding of molecular processes induced by xenobiotics in the ovary.Electronic supplementary materialThe online version of this article (10.1186/s40104-018-0288-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of long non-coding RNAs in porcine granulosa cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Ruszkowska

Nynca

Paukszto

et al. 2018

J Animal Sci Biotechnol

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“…Molcan et al. () modelled the binding of TCDD, PeCDD, a hexa‐CDD, tri‐ and di‐CDD to porcine CYP1A1 and showed that TCDD has the strongest binding activity. It was also shown that TCDD had the longest distance to the active site of the enzyme, a potential explanation for the very poor degradation.…”

Section: Assessmentmentioning

confidence: 99%

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

121

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The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL‐PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre‐ and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005‐TEQ/g fat in blood sampled at age 9 years based on PCDD/F‐TEQs. No association was observed when including DL‐PCB‐TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F‐TEQ only was on average 2.4‐ and 2.7‐fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL‐PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.

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“…The use of such resolution-dependent approaches is common despite their unreliable, inconsistent, and sometimes conflicting results [21]. We observe that VOIDOO is still popular in diverse disciplines [22,23,24,25,26,27,28,29,30,31,32] and studies of grid-based algorithms continues [33]. The absence of an overarching analytical theory is because individual researchers have focused on problem-specific, local aspects of geometry problems, concentrating on isolated issues such as surfaces, voids, channels, volumes, areas, and so on.…”

Section: Introductionmentioning

confidence: 98%

MGOS: A Library for Molecular Geometry and its Operating System

Kima¹,

Ryua²,

Choa³

et al. 2019

Preprint

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The geometry of atomic arrangement underpins the structural understanding of molecules in many fields. However, no general framework of mathematical/computational theory for the geometry of atomic arrangement exists. Here we present "Molecular Geometry (MG)" as a theoretical framework accompanied by "MG Operating System (MGOS)" which consists of callable functions implementing the MG theory. MG allows researchers to model complicated molecular structure problems in terms of elementary yet standard notions of volume, area, etc. and MGOS frees them from the hard and tedious task of developing/implementing geometric algorithms so that they can focus more on their primary research issues. MG facilitates simpler modeling of molecular structure problems; MGOS functions can be conveniently embedded in application programs for the efficient and accurate solution of geometric queries involving atomic arrangements. The use of MGOS in problems involving spherical entities is akin to the use of math libraries in general purpose programming languages in science and engineering.

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Structural-functional adaptations of porcine CYP1A1 to metabolize polychlorinated dibenzo-p-dioxins

Cited by 11 publications

References 68 publications

Identification and characterization of long non-coding RNAs in porcine granulosa cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Identification and characterization of long non-coding RNAs in porcine granulosa cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

MGOS: A Library for Molecular Geometry and its Operating System

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