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Xanthine Dehydrogenase Is a Modulator of Dopaminergic Neurodegeneration in Response to Bacterial Metabolite Exposure in C. elegans.
Thies, Jennifer L; Willicott, Karolina; Craig, Maici L; Greene, Madeline R; DuGay, Cassandra N; Caldwell, Guy A; Caldwell, Kim A.
Afiliación
  • Thies JL; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.
  • Willicott K; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.
  • Craig ML; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.
  • Greene MR; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.
  • DuGay CN; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.
  • Caldwell GA; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.
  • Caldwell KA; Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cells ; 12(8)2023 04 15.
Article en En | MEDLINE | ID: mdl-37190079
ABSTRACT
Oxidative stress is a contributing factor to Parkinson's disease (PD). Considering the prevalence of sporadic PD, environmental exposures are postulated to increase reactive oxygen species and either incite or exacerbate neurodegeneration. We previously determined that exposure to the common soil bacterium, Streptomyces venezuelae (S. ven), enhanced oxidative stress and mitochondrial dysfunction in Caenorhabditis elegans, leading to dopaminergic (DA) neurodegeneration. Here, S. ven metabolite exposure in C. elegans was followed by RNA-Seq analysis. Half of the differentially identified genes (DEGs) were associated with the transcription factor DAF-16 (FOXO), which is a key node in regulating stress response. Our DEGs were enriched for Phase I (CYP) and Phase II (UGT) detoxification genes and non-CYP Phase I enzymes associated with oxidative metabolism, including the downregulated xanthine dehydrogenase gene, xdh-1. The XDH-1 enzyme exhibits reversible interconversion to xanthine oxidase (XO) in response to calcium. S. ven metabolite exposure enhanced XO activity in C. elegans. The chelation of calcium diminishes the conversion of XDH-1 to XO and results in neuroprotection from S. ven exposure, whereas CaCl2 supplementation enhanced neurodegeneration. These results suggest a defense mechanism that delimits the pool of XDH-1 available for interconversion to XO, and associated ROS production, in response to metabolite exposure.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Xantina Deshidrogenasa / Caenorhabditis elegans Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cells Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Xantina Deshidrogenasa / Caenorhabditis elegans Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cells Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos