Degree Name

MS (Master of Science)

Program

Biology

Date of Award

5-2023

Committee Chair or Co-Chairs

Patrick Bradshaw

Committee Members

Tyrone Genade, Chad Fraiser

Abstract

Reactive oxygen species (ROS) such as H2O2 can damage cellular components and are formed as a byproduct of mitochondrial oxidative metabolism. Studies using the nematode C. elegans have found that increasing ROS during development or early adulthood can extend lifespan, while increasing ROS during later adulthood normally decreases lifespan. NADPH provides the reducing power for several cellular antioxidants and is synthesized in a two-step reaction from NAD+ with the first step being catalyzed by NAD kinase (NADK). In this study, the effects of knocking down C. elegans cytoplasmic NADK, nadk-1 globally or in a neuron or intestine-specific manner starting from early development on oxygen consumption and ROS levels were determined. Surprisingly, whole body knockdown of nadk-1 to decrease cytoplasmic NADPH levels decreased oxygen consumption and tert-butyl hydroperoxide-stimulated ROS levels, which was phenocopied by intestine-specific or neuron-specific knockdown. Thioredoxin reductase measurements following nadk-1 knockdown showed a trend toward increased activity.

Document Type

Thesis - unrestricted

Copyright

Copyright by the authors.

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