| Grant number: | 10/06345-1 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | August 01, 2010 |
| End date: | November 30, 2013 |
| Field of knowledge: | Agronomical Sciences - Veterinary Medicine - Animal Pathology |
| Principal Investigator: | Catarina de Fatima Pereira Teixeira |
| Grantee: | Elbio Leiguez Junior |
| Host Institution: | Instituto Butantan. São Paulo , SP, Brazil |
| Associated research grant: | 08/57898-0 - National Institute of Science and Technology on Toxins, AP.TEM |
| Associated scholarship(s): | 12/06730-8 - Study of the role of PLIN2 in inflammatory response induced by MT-III, a Phospholipase A2 isolated from Bothrops asper snake venom: lipid bodies biogenesis and release of inflammatory mediators, BE.EP.DR |
Abstract The Bothrops venoms contain high concentrations of secreted phospholipase A2 (sPLA2), which have structural and functional homology with the mammalian PLA2s whose levels are increased in inflammatory diseases such as atherosclerosis. Recently we demonstrated that MT-III, a sPLA2, induced an increase in lipid bodies formation and expression of ADRP, a structural protein member of the PAT family which plays a key role in lipid body assembling, adipocyte differentiation and foam cells formation. However, the mechanisms involved in ADRP expression and lipid accumulation and synthesis induced by MT-III in macrophages remain unknown. Thus, this study will assess MT-III-effects I) on intracellular accumulation of triacylglycerol and cholesterol; II) on gene expression of enzymes involved in triacylglycerol and cholesterol synthesis; III) on activation and expression of PPAR-gama, PPAR-delta, CD36 receptors and IV) on activation and expression of transcription factor SREBP-2 in macrophages. The involvement of PPAR-gama, PPAR-delta and CD36 in lipid bodies formation and ADRP expression, induced by MT-III, in macrophages will also be assessed. In this sense, this work will promote a better understanding of the inflammatory reaction induced by Bothrops venoms. Moreover, this study will contribute to the understanding of actions of this family of enzymes in inflammatory processes and those related to lipid metabolism. Additionally, this study may reveal new therapeutics targets in diseases which lipid imbalance is a major factor. (AU) | |
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