Nagashree Shridhar Bhat / Chemistry & Biochemistry / Faculty Mentor: Subhrangsu Mandal
Inflammation is a type of immune response against pathogenic invasion. Macrophages, being the essential players in immune response, undergo metabolic reprogramming resulting in increased tryptophan catabolism and disrupted cholesterol homeostasis. Normally, cholesterol, internalized by LDL (Low density lipoprotein) receptors in macrophages, gets esterified by ACAT1 (Acetyl-CoA acetyltransferase) enzyme. Excessive esterification of cholesterol may lead to atherosclerosis and cardiovascular diseases. Our recent study demonstrated that one of the HDL (High density lipoproteins) transporters, Scavanger receptor B I (SR-B1) expression, as well as cholesterol uptake are downregulated in human THP1 derived macrophages (THP1-Mφ) treated with LPS (lipopolysaccharide from bacteria), indicating an association between inflammation and disrupted cholesterol transport in macrophages. Furthermore, in a preliminary study, we observed that ACAT1 expression is significantly increased upon LPS mediated inflammation in macrophages. Additionally, in a separate study, peroxidized lipid level, a marker of oxidative stress, was elevated in inflamed macrophages. Based on these findings, we propose to elucidate the mechanism of modified-LDL receptors and de-esterification enzymes in cholesterol homeostasis under inflammation. We also aim to explore the link between tryptophan catabolism and cholesterol transport which will lead to the discovery of biomarkers for cardiovascular diseases.
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