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Browsing by Author "Dolan, Connor Cathal, author"

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    Comparative analysis of the role of redox active molecules on bioenergetically active membranes
    (Colorado State University. Libraries, 2024) Dolan, Connor Cathal, author; Crans, Debbie, advisor; Kennan, Alan, committee member; Chicco, Adam, committee member
    Transition metals play crucial roles in various biological processes, with vanadium and manganese being prominent examples due to their redox activity and impact on oxidative stress, mitochondrial function, and disease progression. This manuscript focuses on the role of transition metals, particularly vanadium, in biological functioning, with an emphasis on oxidative stress and mitochondria. Chapter 1 of this thesis discusses the respective role that vanadium plays on oxidative stress and how that influences biological systems. Due to its variety of speciation states and its ability to redox cycle as well as its structural and electronic properties, vanadium can affect biological systems in a variety of ways. These include the generation of reactive oxygen species, lipid peroxidation, protein inhibition, changes in membrane fluidity and potential. DNA damage and cell death. The effects that vanadium has is highly dependent on the speciation and state that they exist in. this can impact the system that is being affected and the outcome. Species such as decavanadate have a unique and profound biological effect. Changing of the species, oxidation state and complexation can alter the biological consequences associated with vanadium. Chapter 2 of this thesis explores the differences and similarities between vanadium and manganese on cardiac mitochondrial dysfunction and oxidative stress. Using varying vanadium and manganese compounds, we investigated the effects they had on isolated cardiac mitochondria using high resolution respirometry and UV-Vis spectroscopy. We found similarities between metal salts on inhibition of respiration as well as significant differences on the metals iii effect on mitochondrial swelling. We further investigated the role of transport proteins on vanadium induced swelling and found that the mitochondrial calcium uniporter played an important role in vanadium induced mitochondrial swelling. We further investigated the differences in species and oxidation state on function. We tested the difference between VV and VIV on mitochondrial swelling and found that VIV led to significantly greater swelling. We also found that there the VO(OH)3 - monomer and dimer were present in both VIV compounds and the Mn2+ ion was present in both manganese compounds. This speciation similarity between compounds may account for some of the similar effects seen within the same metal compounds as well as the differences seen when comparing manganese and vanadium together.