Interactions between the glutathione pathway enzymes and tobacco smoke exposure on lung function outcomes and asthma related phenotypes

Jasminka Murdzoska

    Research output: ThesisDoctoral Thesis

    177 Downloads (Pure)

    Abstract

    [Truncated abstract] It is well recognised that complex diseases such as asthma, atopy and other related phenotypes are influenced by genetic factors and environmental exposures. While exposure to different environmental agents (e.g. inhaled pollutants) may trigger respiratory symptoms, an individual’s response to such exposures is likely to be determined by genetic variations affecting detoxification enzymes. Genetic determinants could then explain the apparent high degree of inter-individual variability in susceptibility to respiratory disease. The enzymes involved in the glutathione detoxification pathway are important in environmentally related diseases due to their ability to detoxify harmful compounds such as polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke. These enzymes therefore play a role in modulating the harmful effects of reactive oxygen species and oxidative stress. The enzymes that form part of the glutathione detoxification pathway include glutathione reductase (GR) and glutathione peroxidase (GPx), which are involved in the glutathione redox cycle replenishing intracellular glutathione; glutamate cysteine ligase (GCL), which is involved in the synthesis of glutathione; and glutathione S-transferases (GSTs), which catalyse the conjugation of xenobiotics to glutathione to facilitate excretion from the body. Genetic variations in the genes encoding these enzymes have been associated with altered enzyme activity and respiratory diseases such as asthma and lung cancer. Additionally, levels of glutathione including the ratio of reduced to oxidised glutathione (GSH/GSSG) can be used as an indicator of oxidative stress status. Decreased GSH and increased GSSG levels have been associated with increased oxidative stress...
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2011

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