Browsing by Subject "Lipids"

Now showing 1 - 4 of 4

Identification and Characterization of Caveolins in Mouse Macrophages
(2002-12-01) Gargalovic, Peter; Dory, Lad; Basu, Alakananda; McConathy, Walter
Peter Gargalovic, Identification and Characterization of Caveolins in Mouse Macrophages. Doctor of Philosophy (Biochemistry and Molecular Biology), December 2002, 206 pp., 3 tables, 41 illustrations, references, 296 titles. The understanding of the mechanisms which control macrophage-lipid management, and their accumulation in atherosclerotic lesions, is of significant importance. Caveolins are proteins associated with cholesterol-rich membrane domains and are intimately linked to the regulation of lipid metabolism and transport. The expression and function of caveolin proteins in three macrophage cell types: thioglycollate-elicited mouse peritoneal macrophages, resident mouse peritoneal macrophages and the J774 macrophage cell line. Data in this work establish that the primary macrophages express caveolin-1 and -2, while J774 cells express only caveolin-2. Immunofluorescence microscopy studies indicate that caveolins in primary macrophages do not colocalize, with caveolin-1 being present on the cell surface and cavelon-2 in the Golgi compartment. Analysis of macrophages also showed that caveolin-1, but not caveolin-2, is present in detergent insoluble lipid raft membranes. While caveolin expression in macrophages is not regulated by sterols, both caveolin isoforms can be secreted from cholesterol-loaded macrophages in the presence of high-density lipoprotein (HDL). Secreted caveolins are part of the complex that has a density similar to HDL, which suggests their association with HDL and potentially a role in HDL-mediated reverse cholesterol transport. The examination of caveolin expression in macrophages shows that caveolin-1, but not caveolin-2 expression is highly upregulated by agents that induce apoptosis in these cells. Induction of caveolin-1 expression precedes DNA fragmentation, is independent of caspase activation, and correlates with the exposure of phosphatidylserine on the cell surface. Importantly, immunofluorescence analysis determined that caveolin-1 in lipid rafts colocalizes extensively with phosphatidylserine present on the surface of apoptotic cells. This study thus identifies caveolin-1 as a specific and early marker of the macrophage apoptotic phenotype. Findings here strongly implicate the involvement of caveolin-1 and lipid rafts in the changes of plasma membrane lipid composition as well as involvement in efficient clearance of apoptotic cells by a phosphatidylserine-mediated mechanism.
Liver Biomarkers and Lipid Profiles in Mexican and Mexican-American 10- to 14-Year-Old Adolescents at Risk for Type 2 Diabetes
(Hindawi, 2017-07-26) Fernández-Gaxiola, Ana Cecilia; Valdés-Ramos, Roxana; Fulda, Kimberly G.; López, Ana Laura Guadarrama; Martínez-Carrillo, Beatriz E.; Franks, Susan F.; Fernando, Shane I.
Liver enzymes alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) are markers for type 2 diabetes mellitus (T2DM); alkaline phosphatase is a marker of liver disease. Mexican-American adolescents are disproportionately affected by T2DM, while in Mexico its prevalence is emerging. We assessed liver biomarkers and lipid profiles among Mexican and Mexican-American adolescents 10-14 years old with high/low risk of T2DM through a cross-sectional, descriptive study (Texas n = 144; Mexico n = 149). We included family medical histories, anthropometry, and blood pressure. Obesity was present in one-third of subjects in both sites. ALT (UL) was higher (p < 0.001) in high-risk adolescents (23.5 ± 19.5 versus 17.2 ± 13.4 for males, 19.7 ± 11.6 versus 15.1 ± 5.5 for females), in Toluca and in Texas (26.0 ± 14.7 versus 20.0 ± 13.2 for males, 18.2 ± 13.4 versus 14.6 ± 10.1 for females), as well as GGT (UL) (p < 0.001) (18.7 ± 11.1 versus 12.4 ± 2.3 for males, 13.6 ± 5.8 versus 11.5 ± 3.9 for Mexican females; 21.0 ± 6.8 versus 15.4 ± 5.5 for males, 14.3 ± 5.0 versus 13.8 ± 5.3 for females in Texas). We found no differences by sex or BMI. Total cholesterol and HDL were higher among Mexican-Americans (p < 0.001). In conclusion, multiple risk factors were present in the sample. We found differences by gender and between high and low risk for T2DM adolescents in all liver enzymes in both sites.
N-Acylethanolamine Signaling in Neurons
(2008-12-01) Duncan, Raymond Scott; Koulen, Peter; Simpkins, James; Forster, Michael
Duncan, Raymond S., N-acylethanolamine signaling in neurons. Doctor of Philosophy (Biomedical Sciences), December 2008, 356 pp., 1 table, 70 illustrations, bibliography, 576 titles. Neurodegenerative diseases including Alzheimer’s disease are and will continue to be significant health problems as the aging population increases. The maintenance of neuronal calcium homeostasis has been a focus in degenerative disease research for many years. Within the last several years, lipids that activate cannabinoid receptors, and thus called cannabinoids, have gained recognition as neuroprotectants in models of neurodegenerative diseases. A subset of these cannabinoids, the N-acylethanolamines (NAEs), includes the well characterized neuroprotective lipid, arachidonylethanolamine. Other NAEs, such as palmitoylethanolamine (PEA), are more abundant in neurons and do not activate cannabinoid receptors, suggesting other targets for these lipids exist. Since non-cannabinoid NAEs rapidly accumulate after neuronal injury, it is likely they play a role in cellular responses to injury. Interestingly, some NAEs can alter intracellular Ca2+ signaling, but the underlying mechanism of action remains unclear. I hypothesized that the non-cannabinoid NAEs, such as PEA, protect the hippocampal cell line, HT22, from oxidative stress in part by reducing intracellular calcium release. I determined that HT22 cells and cultured mouse cortical neurons express proteins involved in NAE signaling, thus warranting the use of pharmacological inhibitors of these proteins in subsequent neuroprotection studies. Using HT22 cells, I determined that PEA exhibitis antiproliferative effects and neuroprotects against oxidative stress. In addition, I determined that PEA facilitates the nuclear translocation of putative protective proteins that can be regulated by Ca2+ through a mechanism not involving cannabinoid receptor activation. These findings led me to hypothesize that PEA alters release of Ca2+ from intracellular stores. To test this hypothesis, I determined that our cell models express inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) both of which are intracellular Ca2+ channels elevated in response to oxidative stress. I determined that treatment of HT22 cells with PEA reduced intracellular Ca2+ release elicited by chemical depolarization with KCI. My results suggest that non-cannabinoid NAEs, such as PEA, protect the hippocampal cell line, HT22, from oxidative stress in part by activating putative neuroprotective signaling proteins and by reducing intracellular calcium release.
Statins and PCSK9 Inhibitors: How They Have Shaped Medicine, A Comparative Review
(2016-12-01) Escarsega, Phillip R.; Rustin E. Reeves; Patricia A. Gwirtz
Keeping serum low density lipoprotein cholesterol (LDL-C) levels within recommended ranges has been proven to lower the risk of cardiovascular events from occurring. To lower LDL-C levels, statins have been the drug of choice for the last few decades since they were introduced. However, the discovery of PCSK9 inhibitors and new knowledge about how they are able to lower LDL-C levels may provide physicians a new path to consider when choosing a course of treatment in patients that fit the criteria for PCSK9 inhibition. Furthermore, there are several risks with statins which may turn physicians towards using PCSK9 inhibitors in patients with uncontrolled LDL-C. This practicum report is a review of the latest developments in PCSK9 drugs and how they compare to statins in lowering LDL levels.