Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13/2F1-Humanized Mice

Conclusion: CYP2F1 is an active enzyme. Both CYP2A13 and CYP2F1 are active toward NA in the CYP2A13/2F1-humanized mice, where they play significant roles in NA-induced respiratory tract toxicity. https://doi.org/10.1289/EHP844 Received: 20 July 2016 Revised: 22 October 2016 Accepted: 07 November 2016 Published: 08 June 2017 Address correspondence to L. Van Winkle, Center for Health and the Environment, Building 3792, Room 129, Old Davis Rd., UC Davis, Davis, CA 95616 USA. Telephone: (530) 754-9060. E-mail: lsvanwinkle@ucdavis.edu , and X. Ding, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Rd., NanoFab East, Albany, NY 12203 USA. Telephone: (518) 956-7057. E-mail: xding@sunypoly.edu Supplemental Material is available online (https://doi.org/10.1289/EHP844). The authors declare they have no actual or potential competing financial interests. Note to readers with disabilities: EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact ehponline@niehs.nih.gov. Our staff will work with you to assess and meet your accessibility needs within 3 working days. Supplemental Material PDF (166 KB) Note to readers with disabilities: EHP has provided a 508...
Source: EHP Research - Category: Environmental Health Authors: Tags: Research Source Type: research

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AbstractMutations in theCDKL5 gene, which encodes a serine/threonine kinase, causes a rare encephalopathy, characterized by early-onset epilepsy and severe intellectual disability, named CDKL5 deficiency disorder (CDD). In vitro and in vivo studies in mouse models of Cdkl5 deficiency have highlighted the role of CDKL5 in brain development and, in particular, in the morphogenesis and synaptic connectivity of hippocampal and cortical neurons. Interestingly, Cdkl5 deficiency in mice increases vulnerability to excitotoxic stress in hippocampal neurons. However, the mechanism by which CDKL5 controls neuronal survival is far fro...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
In this study, we investigated the anti-apoptotic function of serpina3k in vivo using a mouse model of TBI, as well as the underlying neuroprotective mechanism in vitro using the SH-SY5Y human neuroblastoma cell line. TBI was induced in adult male C57BL/6 mice using controlled cortical impact. Serpina3k protein was intravenously administered at a concentration of 0.5 mg/kg twice daily for up to 14 days. SH-SY5Y cells were subjected to biaxial stretch injury and then treated with different concentrations of serpina3k. We found that endogenous serpina3k protein levels were elevated in peri-contusion areas of the mouse brain ...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
AbstractParkinson ’s disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of dopaminergic neurons in substantia nigra. The underlying mechanisms of PD pathogenesis have not been fully illustrated and currently PD remains incurable. Accumulating evidences sugges t that mitochondrial dysfunction plays pivotal role in the dopaminergic neuronal death. Therefore, discovery of novel and safe agent for rescuing mitochondrial dysfunction would benefit PD treatment. Here we demonstrated for the first time that α-Arbutin (Arb), a natural polyphenol extracted fromEric...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research
Publication date: Available online 2 August 2019Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Valentina Gumina, Claudia Colombrita, Claudia Fallini, Patrizia Bossolasco, Anna Maria Maraschi, John E. Landers, Vincenzo Silani, Antonia RattiAbstractThe RNA-binding protein TDP-43, associated to amyotrophic lateral sclerosis and frontotemporal dementia, regulates the alternative splicing of several genes, including the skipping of TNIK exon 15. TNIK, a genetic risk factor for schizophrenia and causative for intellectual disability, encodes for a Ser/Thr kinase regulating negatively F-actin d...
Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - Category: Genetics & Stem Cells Source Type: research
Nagore Elu1, Nerea Osinalde2, Javier Beaskoetxea1, Juanma Ramirez1, Benoit Lectez1, Kerman Aloria3, Jose Antonio Rodriguez4, Jesus M. Arizmendi1 and Ugo Mayor1,5* 1Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain 3Proteomics Core Facility-SGIKER, University of the Basque Country (UPV/EHU), Leioa, Spain 4Department of Genetics, Physical Anthropology and Animal Physiology, University of ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
In conclusion, we further advanced the molecular understanding of mitochondrial dysfunction in RTT. Intensified mitochondrial O2 consumption, increased mitochondrial ROS generation and disturbed redox balance in mitochondria and cytosol may represent a causal chain, which provokes dysregulated proteins, oxidative tissue damage, and contributes to neuronal network dysfunction in RTT. Introduction Rett syndrome (RTT) is a progressive neurodevelopmental disorder. It primarily affects females, who show the first obvious symptoms within 6–18 months after birth. Among the characteristics are a regression of mental ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion: These results suggest intelectin-1 promotes angiogenesis, inhibits oxidative stress and reduces apoptosis by stimulating the Akt-eNOS signaling pathway in response to ischemia in vitro. Introduction Stroke is a main reason of human neurological disability, ischemic stroke (IS) accounts for almost 80–90% of all strokes. IS occurs after a cerebral blood flow disruption, leading to cellular death and tissue damage by restricting glucose and oxygen supplies (1). Ischemic vascular diseases cause substantial vascular valve and vascular endothelial cell injuries, eventually damaging the surrounding tissu...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
This study aims at investigating the still poorly clear pathogenesis of migraine and the potential role of anti-CGRP mAbs in the scenario of prophylaxis of migraine. Introduction: Migraine Clinic Migraine consists in unilateral headache accompanied by a cluster of other sensory, autonomic and cognitive symptoms and it has been identified by the global burden of disease (GBD) study 2016 as the sixth most prevalent disorder and one of the main causes of disability all over the world, often occuring in working age and in young adult and middle-aged women (Collaborators, 2018). Hence, migraine represents a very serious...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research
RASopathies are a group of rare congenital diseases in which dysregulated signaling through the RAS-MAPK signaling cases is the critical pathogenetic mechanism. This definition excludes postnatally acquired conditions (e.g. RAS-MAPK driven neoplasms) and PIK3-AKT pathway related disorders as well as conditions with only ancillary RAS pathway involvement (e.g. KAT6B-, RAP1A/B-related disorders). The definition, however, includes the following categories: (1) Noonan syndrome and related disorders, specifically Noonan syndrome (NS), NS with multiple lentigines, NS-like disorder with loose anagen hair, CBL syndrome, cardiofaci...
Source: Blood - Category: Hematology Authors: Tags: A MAP(K) to Pediatric RASopathies Source Type: research
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