Browsing by Author "Sher, Lucien"
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- ItemThe endothelium: an essential barrier between chronic stress and vascular pathology(Stellenbosch : Stellenbosch University, 2019-12) Sher, Lucien; Essop, M. Faadiel; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.ENGLISH ABSTRACT: In recent years, chronic stress has emerged as an influential and understudied risk factor for the onset of cardiovascular disease. While much is known regarding the physiological systems that orchestrate the innate stress response, limited knowledge exists regarding the molecular derangements that underpin cardiovascular pathologies. Endothelial integrity is essential for maintaining a stable internal environment. Stress-mediated cardiovascular, metabolic and immunologic alterations negatively impact the vaso-reactive capabilities of the endothelium. Furthermore, chronically elevated circulating levels of glucocorticoids and catecholamines not only directly influence nitric oxide availability but further contribute towards a proinflammatory and prooxidative state. A dysfunctional endothelial layer in turn facilitates the development of stenotic and atherosclerotic vascular lesions. This review highlights the current burden of chronic stress globally and in South Africa. We subsequently discuss the activity and regulation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system following exposure to acute and chronic stressors. Lastly, we focus on mechanistic avenues that contribute towards endothelial dysfunction and a compromised cardiovascular system.
- ItemThe impact of sugar-sweetened beverage consumption on the liver : a proteomics-based analysis(MDPI, 2020) Benade, Janina; Sher, Lucien; De Klerk, Sheneez; Deshpande, Gaurang; Bester, Dirk; Marnewick, Jeanine L.; Sieck, Gary; Laher, Ismail; Essop, M. FaadielCardiometabolic complications such as the metabolic syndrome and Type 2 Diabetes Mellitus (T2DM) are major causes of global morbidity and mortality. As sugar-sweetened beverages (SSBs) are implicated in this process, this study aimed to obtain greater mechanistic insights. Male Wistar rats (~200 g) were gavaged with a local SSB every day for a period of six months while the control group was gavaged with an iso-volumetric amount of water. Experimental dosages were calculated according to the surface area-to-volume ratio and were equivalent to 125 mL/day (in human terms). A proteomic analysis was performed on isolated liver samples and thereafter, markers of endoplasmic reticulum (ER) stress, antioxidant/oxidant capacity, calcium regulation, and mitochondrial functionality were assessed. These data show that SSB consumption resulted in (a) the induction of mild hepatic ER stress; (b) altered hepatic mitochondrial dynamics; and (c) perturbed calcium handling across mitochondria-associated ER membranes. Despite significant changes in markers of ER stress, the antioxidant response and calcium handling (proteomics data), the liver is able to initiate adaptive responses to counteract such stressors. However, the mitochondrial data showed increased fission and decreased fusion that may put the organism at risk for developing insulin resistance and T2DM in the longer term.