Preliminary data suggests that the lipogenic factor Acylation Stimulating Protein (ASP), stimulates the activity of calcium-dependent phospholipase A2 (cPLA2) by increasing intracellular calcium levels [Ca2+]i and by activating extracellular-signal-regulated kinase 1/2 (ERK 1/2). The arachidonic acid (AA) generated by cPLA2 action appears to function as a second messenger in ASP signaling. / ASP also blocks TG breakdown. The calcium-independent PLA2 (iPLA2) zeta has recently been identified as a novel TG-lipase in 3T3-L1 cells. Bromoenol lactone (BEL), a non-reversible iPLA2 inhibitor, has been shown to specifically inhibit the TG-lipase activity of this enzyme. Preliminary data demonstrates that BEL stimulates basal TG synthesis, likely by inhibiting TG breakdown. The effects of BEL in combination with ASP are non-additive, suggesting they act through the same pathway. Furthermore, ASP appears to inhibit 3H-AA release into the media in a concentration-dependent manner. We propose that ASP inhibits an iPLA2 isoform with TG-lipase activity, an effect that can be mimicked by BEL.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.84051 |
| Date | January 2005 |
| Creators | Legakis, Helen |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002261934, proquestno: AAIMR22743, Theses scanned by UMI/ProQuest. |
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