Multi-Well Extracellular Flux Analyzer for Mitochondrial Stress Arrays
Abstract
Major Goals: Project 1: Metabolic reprogramming induced by environmental exposures Project 1A: Modulation of metabolism by environmental toxicants BPA induces a wide variety of cellular effects, though two common mechanisms have been found across tissues and organisms. These mechanisms are epigenetic reprogramming and oxidative stress. Our interest has been in oxidative stress induced by BPA. As part of this work, we have noted BPA induces oxidative stress, specifically within the mitochondrial compartment. This mitochondrial-specific stress could damage mitochondrial DNA and initiate bioenergetic changes that contribute to obesity and cancer development. Importantly, while other studies have noted mitochondrial stress in the presence of physiologically relevant concentrations of BPA (10-100 nM), no mechanistic study of bioenergetic changes has been conducted. The dedicated Seahorse instrument will support our investigations into the metabolic-specific effects of BPA and their impact on mitochondrial function. In addition to studies involving BPA, our laboratory has begun investigating DHA, the active ingredient in sunless tanning agents. DHA is also produced by electronic cigarette (e-cigarette) vapor. Similar to tobacco cigarettes, e-cigarettes can have long-term health consequences for users. However, there are additional unknown health effects from the flavoring agents used in these products. DHA is a three-carbon sugar in e-cigarette vapor produced by the combustion of other flavoring agents. DHA can be phosphorylated by cells to DHAP (dihydroxyacetone phosphate) and enter glycolytic pathways. We previously determined that doses of DHA, consistent with consumer exposures to sunless tanning products, induced senescence and apoptosis a melanoma cell line. Given that e-cigarette use could result in micromolar to millimolar systemic exposure, we are examining the metabolic changes induced by DHA exposure in lung, liver, and kidney model cell lines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 31, 2021
- Accession Number
- AD1221890
Entities
People
- Jennifer M. Scalici
- Marie E. Migaud
- Natalie R. Gassman
Organizations
- University of South Alabama