Browsing by Author "Breytenbach, Jacomi Heidi"

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    Exploring the interactions of hyperglycaemia, SARS-CoV-2 spike protein & iron in HepG2 cells
    (Stellenbosch : Stellenbosch University, 2024-03) Breytenbach, Jacomi Heidi; Nell, Theo A. ; Joseph, Danzil; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Medical Physiology.
    ENGLISH ABSTRACT: Background: Diabetic COVID-19 patients have increased severity, disease progression and mortality, as well as an increased risk to develop persisting symptoms. Hyperglycaemia could be a central driving force of the pathophysiology in diabetic COVID-19 patients, demonstrating a multifactorial interaction with metabolic abnormalities, immune dysfunction, and dysregulated iron metabolism. An intricate relationship between hypoxia inducible factor 1, iron and cellular metabolism was also uncovered. Considering the need for a greater mechanistic understanding regarding this interplay, an in vitro investigation into the interaction between glucose and SARS-CoV2 Spike protein (protein involved in viral entry) and the effect of this on HIF-1 activation, iron and inflammatory parameters was therefore undertaken. Methods: HepG2 cells were cultured, and the following treatment groups were allocated: Low glucose (LG), High glucose (HG), Vehicle control (DMSO), LG + Spike protein, HG + Spike protein, HG + Prolyl Hydroxylase Inhibitor (PHI) (HIF-1α stabilizer), and HG + PHI + Spike protein. Various assays were used to assess cell viability, and production of reactive oxygen species (ROS). Western Blots were employed to measure iron, inflammatory, metabolic, and viral entry factor expression. Results: Significant decreases in ferritin levels were observed in HG + Spike, and HG + PHI treatment groups, indicating an interesting interaction between glucose and SARS-CoV-2 Spike that could underly attenuated circulating iron in COVID-19 patients. No significant differences in ROS, or inflammatory parameters were noted between different groups, indicating a lack of an inflammatory response, potentially mediated by low levels of intracellular iron. Lastly, stabilization of HIF-1α, as well as protein expression in different groups, could not be determined due to protein fragmentation. Conclusion: A remarkable interaction between glucose and Spike was associated with lower intracellular ferritin levels, independent of inflammation, necessitating more research.