Masters Degrees (Physiological Sciences)

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Browsing Masters Degrees (Physiological Sciences) by Author "Cairns, Megan Louise"

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    Exploring mechanisms underlying stress-related cardiometabolic complications
    (Stellenbosch : Stellenbosch University, 2022-03) Cairns, Megan Louise; Essop, M. Faadiel; Joseph, Danzil; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Introduction: Cardiometabolic diseases (CMD) constitute a major, global burden of disease. Of concern, psychosocial stress is an emerging risk factor for cardiovascular diseases onset. Although associations between psychological complications and CMD are well established, the underlying mechanisms driving this process require further investigation. Oxidative stress is linked to both chronic stress and CMD progression and can elicit detrimental sequelae. For example, it can augment PARP activity and thereby shunt glycolytic intermediates into the hexosamine biosynthetic pathway (HBP). Increased HBP flux can in turn lead to dysregulated O-GlcNAcylation of target proteins, thereby potentiating cardiometabolic complications. As excessive HBP flux is observed in a range of CMD, we hypothesized that increased oxidative stress and HBP activation play a key role in stress-mediated CMD onset and progression. Our main objective was to assess the degree of total protein O-GlcNAcylation and redox status of cardiac tissues isolated from stressed versus control rats. Methods: This preclinical study exposed male Wistar rats (n = 14 per group) to 9.5 weeks of unpredictable chronic mild stressors versus non-stressed controls. Behavioral tests were initially conducted to assess the presence of depression and anxiety. Post- euthanasia, plasma corticosterone, and epinephrine levels were evaluated, while myocardial redox state, glucocorticoid receptor expression, and activity, as well as HBP activation, were also determined. Results: Stressed rats displayed an anxious phenotype, with lowered plasma corticosterone levels (p = 0.0394 vs. controls) and higher plasma epinephrine concentrations (p = 0.0284 vs. controls). Our data revealed increased cardiac lipid peroxidation (p = 0.0421 vs. controls) but without any alterations in antioxidant defense systems (catalase, total glutathione, and oxygen radical absorbance capacity). Cardiac HBP activation remained unchanged between the experimental groups, with no significant alterations to GFAT1 or O-GlcNAc expression. Conclusion: These data show that the stress protocol triggered an anxious phenotype together with increased myocardial oxidative stress. The elevated oxidative stress may likely occur as a result of increased reactive oxygen species production instead of an impaired antioxidant system. The HBP data suggest that the mild degree of oxidative damage in the heart was insufficient to alter normal glucose metabolism.