Phytochemical Flavone Confers Broad-Spectrum Tolerance to Insecticides in Spodoptera litura by Activating ROS/CncC-Mediated Xenobiotic Detoxification Pathways

Benzoxazolin-2(3H)-one (BOA) is an allelochemical most commonly associated with monocot species, formed from the O-glucoside of 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one by a two-step degradation process. The capacity of Arabidopsis to detoxify exogenously supplied BOA was analyzed by quantification of the major known metabolites BOA-6-OH, BOA-6-O-glucoside, and glucoside carbamate, revealing that detoxification occurs predominantly through O-glucosylation of the intermediate BOA-6-OH, most likely requiring the sequential action of as-yet-unidentified cytochrome P450 and UDP-glucosyltransferase activities. Transcriptional profiling experiments were also performed with Arabidopsis seedlings exposed to BOA concentrations, representing I50 and I80 levels based on root elongation inhibition assays. One of the largest functional categories observed for BOA-responsive genes corresponded to protein families known to participate in cell rescue and defense, with the majority of these genes potentially associated with chemical detoxification pathways. Further experiments using a subset of these genes revealed that many are also transcriptionally induced by a variety of structurally diverse xenobiotic compounds, suggesting they comprise components of a coordinately regulated, broad specificity xenobiotic defense response. The data significantly expand upon previous studies examining plant transcriptional responses to allelochemicals and other environmental toxins and provide novel insights into xenobiotic detoxification mechanisms in plants.

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Effect of amplification of xenobiotic detoxification pathways genes on survival in lung adenocarcinoma versus squamous cell carcinoma bases on the Cancer Genome Atlas provisional database.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e14093 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e14093-e14093

Author(s):

Mohamed Shanshal ◽

Lukman Aderoju Tijani ◽

Fred L. Hardwicke ◽

Hassan Kaleem ◽

Nicholas C. D'Cunha ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

The Cancer Genome Atlas ◽

Signaling Proteins ◽

Xenobiotic Detoxification ◽

Cancer Genome Atlas ◽

Genome Atlas ◽

Detoxification Pathways

e14093 Background: Ral interacting protein (RLIP76) is a stress-responsive anti-apoptotic efflux transporter of the mercapturic acid pathway (MPy). The MPy enzymes are an essential component of the broader xenobiotic detoxification pathways (XDP) that are regulated by p53 (TP53) in response to xenobiotic/oxidative stress. Homozygous Rlip knockout (Rlip-/-) mice are resistant to benzopyrene induced adenocarcinoma and have constitutive activation of p53. The cancer-resistant phenotype of Rlip-/- mice is the diametric opposite of p53 homozygous knockout mice (p53-/-) mice, which die before the age of 24 weeks of spontaneous malignancy. Methods: Our preliminary studies show that creating Rlip deficiency through pharmacological or genetic methods caused all p53-/- mice to remain cancer-free at an unprecedented age of 32 weeks. This degree of cancer prevention has never been observed with any previous pharmacological or genetic intervention in p53-/- mice. Transcriptomic and epigenomic profiling of the cancer-free p53-/- mice revealed that the direction of change in expression of a network of Rlip-linked XDP enzymes and signaling proteins was identical to that in the cancer-resistant Rlip-/- mice. Results: We hypothesized that the activity of this Rlip-linked subset of the XDP enzymes/signaling proteins (designated XMN1) is a determinant of carcinogenic susceptibility caused by p53 loss. To examine this possibility, we queried the TCGA (The Cancer Genome Atlas) database to determine whether components of XMN1 were differentially expressed in human malignancy, and whether this was associated with overall survival. We focused on non-small cell lung cancer because of the high incidence of p53 mutations in these cancers. To our surprise, we found amplification or upregulation of XMN1 components conferred a reduced survival in lung adenocarcinoma but prolonged survival in squamous cell carcinoma. Conclusions: The mechanisms underlying this remarkable diametrically opposite effect on prognosis of are unknown and suggest opposed functions of XMN1 in Squamous verses Adenocarcinoma.

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Xenobiotic detoxification pathways in honey bees

Current Opinion in Insect Science ◽

10.1016/j.cois.2015.03.005 ◽

2015 ◽

Vol 10 ◽

pp. 51-58 ◽

Cited By ~ 111

Author(s):

May R Berenbaum ◽

Reed M Johnson

Keyword(s):

Honey Bees ◽

Xenobiotic Detoxification ◽

Detoxification Pathways

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A Strengths-Based Approach to Autism: Neurodiversity and Partnering With the Autism Community

Perspectives of the ASHA Special Interest Groups ◽

10.1044/persp2.sig1.56 ◽

2017 ◽

Vol 2 (1) ◽

pp. 56-68 ◽

Cited By ~ 8

Author(s):

Amy L. Donaldson ◽

Karen Krejcha ◽

Andy McMillin

Keyword(s):

Broad Spectrum ◽

First Language ◽

Family Members ◽

Community Identity ◽

Speech Language Pathologists

The autism community represents a broad spectrum of individuals, including those experiencing autism, their parents and/or caregivers, friends and family members, professionals serving these individuals, and other allies and advocates. Beliefs, experiences, and values across the community can be quite varied. As such, it is important for the professionals serving the autism community to be well-informed about current discussions occurring within the community related to neurodiversity, a strengths-based approach to partnering with autism community, identity-first language, and concepts such as presumed competence. Given the frequency with which speech-language pathologists (SLPs) serve the autism community, the aim of this article is to introduce and briefly discuss these topics.

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