Avian interspecific differences in VKOR activity and inhibition: Insights from amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1

Nakayama, Shouta M.M.; Morita, Ayuko; Ikenaka, Yoshinori; Kawai, Yusuke; Watanabe, Kensuke; Ishii, Chikako; Mizukawa, Hazuki; Yohannes, Yared Beyene; Saito, Keisuke; Watanabe, Yukiko; Ito, Masaki; Ohsawa, Natsuo; Ishizuka, Mayumi

doi:10.1016/j.cbpc.2019.108635

Cited by 15 publications

(11 citation statements)

References 38 publications

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“…We also confirmed the higher conservation of the warfarin binding motif (TYX) in fish Vkorc1l1 proteins, with most species exhibiting the fully conserved form (TYA motif) in human and mouse Vkorc1, as previously reported in zebrafish (Danio rerio) Vkors [65]. Research studies on protein sequence analysis and functional characterization of Vkors in fish species are scarce compared to the extensive effort made in mammals, [72][73][74][75] and more recently in birds [76]. Taking into account the relevant roles of Vkorc1 and Vkorc1l1 in recycling VK, and thus on vertebrate development and physiology, it may be highly relevant for the aquaculture industry to identify single nucleotide polymorphisms (SNPs) in vkors from important species (including Senegalese sole), toward the selection of breeders with lower VK nutritional requirements and/or more efficient VK recycling.…”

Section: Ssvkorc1 and Ssvkorc1l1 Are Orthologous To Vertebrate Vkorssupporting

confidence: 87%

New Insights on Vitamin K Metabolism in Senegalese sole (Solea senegalensis) Based on Ontogenetic and Tissue-Specific Vitamin K Epoxide Reductase Molecular Data

Beato

Marques

Laizé

et al. 2020

IJMS

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Vitamin K (VK) is a key nutrient for several biological processes (e.g., blood clotting and bone metabolism). To fulfill VK nutritional requirements, VK action as an activator of pregnane X receptor (Pxr) signaling pathway, and as a co-factor of γ-glutamyl carboxylase enzyme, should be considered. In this regard, VK recycling through vitamin K epoxide reductases (Vkors) is essential and should be better understood. Here, the expression patterns of vitamin K epoxide reductase complex subunit 1 (vkorc1) and vkorc1 like 1 (vkorc1l1) were determined during the larval ontogeny of Senegalese sole (Solea senegalensis), and in early juveniles cultured under different physiological conditions. Full-length transcripts for ssvkorc1 and ssvkorc1l1 were determined and peptide sequences were found to be evolutionarily conserved. During larval development, expression of ssvkorc1 showed a slight increase during absence or low feed intake. Expression of ssvkorc1l1 continuously decreased until 24 h post-fertilization, and remained constant afterwards. Both ssvkors were ubiquitously expressed in adult tissues, and highest expression was found in liver for ssvkorc1, and ovary and brain for ssvkorc1l1. Expression of ssvkorc1 and ssvkorc1l1 was differentially regulated under physiological conditions related to fasting and re-feeding, but also under VK dietary supplementation and induced deficiency. The present work provides new and basic molecular clues evidencing how VK metabolism in marine fish is sensitive to nutritional and environmental conditions.

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Section: Ssvkorc1 and Ssvkorc1l1 Are Orthologous To Vertebrate Vkorssupporting

confidence: 87%

New Insights on Vitamin K Metabolism in Senegalese sole (Solea senegalensis) Based on Ontogenetic and Tissue-Specific Vitamin K Epoxide Reductase Molecular Data

Beato

Marques

Laizé

et al. 2020

IJMS

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“…Furthermore, VKOR is more readily inhibited by warfarin in predatory birds (e.g. snowy owl, Bubo scandiacus and great horned owl) than in domestic fowl 43 . Preliminary work with hepatic microsomes from the American kestrel demonstrated that brodifacoum is a more potent inhibitor of VKOR activity than chlorophacinone and warfarin, 44,45 a trend similar to that observed in the laboratory rat.…”

Section: Toxicological Factors Affecting Sensitivity Of Nontarget Avimentioning

confidence: 76%

“…greater binding affinity of inhibitor) than first‐generation compounds (Table 1). 40,41 Detailed studies of VKOR and its inhibition by various ARs are quite limited for birds, with hepatic microsomal activity and its efficiency appearing to be lower in many species of birds compared to the laboratory rat 42,43 . For warfarin, VKOR activity was inhibited in domestic chicken ( Gallus gallus ) to the same extent as in rats at 40‐fold greater concentrations (based on LD 50 estimates, warfarin is as much as 570 times more potent in rodents than in the chicken) 32,42 .…”

Section: Toxicological Factors Affecting Sensitivity Of Nontarget Avimentioning

confidence: 99%

“…While the development and genetic basis of AR resistance in target rats and mice has been a major research activity, 46–49 the potential for VKOR polymorphisms on AR sensitivity among nontarget wildlife has received little attention. The nucleotide sequence for VKOR has only been described for nine avian species (none of which are raptors) in contrast to its sequence (VKORC1, VKORC1L1) being well‐known for hundreds of mammals 43 . The expression ratio of VKORC1 and the often more AR‐resistant VKORC1L1, both of which support vitamin K‐dependent protein carboxylation in mammals, 50 could account for interspecific differences in sensitivity among birds.…”

Section: Toxicological Factors Affecting Sensitivity Of Nontarget Avimentioning

confidence: 99%

“…Absorption, distribution, metabolism and excretion are determinants of internal concentrations, and residues can be useful dose metrics if they in some way reflect the biologically effective dose at the target site. In mammals 50 and in birds, 43 the AR target enzyme VKORC1 is present in many tissues, with expression being greatest in liver. This would seemingly make AR concentration in liver a potentially ideal predictor of toxicity.…”

Section: Toxicological Factors Affecting Sensitivity Of Nontarget Avimentioning

confidence: 99%

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Challenges in the interpretation of anticoagulant rodenticide residues and toxicity in predatory and scavenging birds

Rattner

Harvey

2020

Pest Management Science

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Anticoagulant rodenticides (ARs) are part of the near billion‐dollar rodenticide industry. Numerous studies have documented the presence of ARs in nontarget wildlife, with evidence of repeated exposure to second‐generation ARs. While birds are generally less sensitive to ARs than target rodent species, in some locations predatory and scavenging birds are exposed by consumption of such poisoned prey and, depending on dose and frequency of exposure, exhibit effects of intoxication that can result in death. Evidence of hemorrhage in conjunction with summed hepatic AR residues >0.1–0.2 mg kg−1 liver wet weight are often used as criteria to diagnose ARs as the likely cause of death. In this review focusing on birds of prey and scavengers, we discuss AR potency, coagulopathy, toxicokinetics and long‐lasting effects of residues, and the role of nutrition and vitamin K status on toxicity, and identify some research needs. A more complete understanding of the factors affecting AR toxicity in nontarget wildlife could enable regulators and natural resource managers to better predict and even mitigate risk. Published 2020. This article is a U.S. Government work and is in the public domain in the USA

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Continued Anticoagulant Rodenticide Exposure of Red‐tailed Hawks (Buteo jamaicensis) in the Northeastern United States with an Evaluation of Serum for Biomonitoring

Murray

2020

Enviro Toxic and Chemistry

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Prior studies (2006-2016) in birds of prey admitted to a wildlife clinic in Massachusetts, USA, revealed widespread exposure to second-generation anticoagulant rodenticides (SGARs) among red-tailed hawks (Buteo jamaicensis, RTHAs). Continued monitoring of species for which historic data are available can reveal trends in exposure that aid in evaluating the effectiveness of risk-mitigation measures. While the majority of exposure-monitoring studies utilize liver tissue collected postmortem, antemortem modalities, such as serum analysis, may be desirable for risk assessments in certain populations. However, the sensitivity of serum for detecting anticoagulant rodenticides (ARs) is not well studied. Paired liver and serum samples from 43 RTHAs were evaluated from 2017 to 2019. In liver tissue, 100% of birds were positive for ARs, with the SGARs brodifacoum, bromadiolone, and difethialone identified most frequently; 91% of birds had liver residues of 2 to 4 ARs. These findings represent the highest exposure both to ARs overall and to multiple ARs in RTHAs compared to previous studies. All birds diagnosed with AR toxicosis (n = 14) were positive for ARs in serum; however, all subclinically exposed birds (n = 29) were negative in serum. These data show that exposure to SGARs remains widespread in RTHAs in this geographic area. In addition, although serum analysis is not sensitive for detecting sublethal exposures in RTHAs, it can potentially support a diagnosis of AR toxicosis in conjunction with other consistent signs.

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Avian interspecific differences in VKOR activity and inhibition: Insights from amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1

Cited by 15 publications

References 38 publications

New Insights on Vitamin K Metabolism in Senegalese sole (Solea senegalensis) Based on Ontogenetic and Tissue-Specific Vitamin K Epoxide Reductase Molecular Data

New Insights on Vitamin K Metabolism in Senegalese sole (Solea senegalensis) Based on Ontogenetic and Tissue-Specific Vitamin K Epoxide Reductase Molecular Data

Challenges in the interpretation of anticoagulant rodenticide residues and toxicity in predatory and scavenging birds

Continued Anticoagulant Rodenticide Exposure of Red‐tailed Hawks (Buteo jamaicensis) in the Northeastern United States with an Evaluation of Serum for Biomonitoring

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