Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis in both primary and transformed mast cells. An IC50 was achieved between 1-5μM in both systems, and apoptosis was preceded by mitochondrial dysfunction and caspase release. In addition to apoptosis, our work also uncovered evidence of autophagy, which can serve as a compensatory mechanism during apoptosis. Interestingly, autophagy appeared to be cyto-protective in the primary cells yet cytotoxic in transformed mast cells. These findings offer insight into the mechanisms of mast cell survival and support the possible utility of statins in mast cell-associated allergic and neoplastic diseases.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-5516 |
| Date | 01 January 2016 |
| Creators | Paez, Patrick A |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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