Possible Role of Lipids as Intracelullar Mediators

• Grant number: 93/03498-4
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 1994
• End date: October 31, 1999
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rui Curi
• Grantee: Rui Curi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant(s): 99/01586-0 - Glucose induces an acute increase of superoxide dismutase activity in incubated rat pancreatic islets., PUB.ART; 98/01955-2 - [14c]-fatty acids and [14c]-phospholipids transfer from macrophages to lymphocytes in co-culture., AR.EXT; 97/09725-3 - Philip Newsholme | University College Dublin - Irlanda, AV.EXT; 96/08848-1 - Impairment of insulin secretion in pancreatic islets isolated from walker 256 tumor-bearing rats., PUB.ART

Abstract

Monocytes/macrophages and lymphocytes present high capacity for lipid synthesis and exportation . These metabolites are potent regulators of immune cells function and metabolism. The aim of this research project is to evaluate the cell-to-cell interactions mediated by transfer of lipids. For this purpose, monocytes/macrophages are co-cultured with the following cells: lymphocytes, tumor cells, enterocytes and pancreatic islets. The following lipids are studied: palmitate, oleate, linoleate, arachidonate, cholesterol and phosphatidylcholine. The experiments are performed using 14C and 3H labelled lipids. The studies up to now performed indicate a significant transfer of arachidonic acid and cholesterol from macrophages to lymphocytes. The effects of the lipid transfer on metabolism and function of the acceptor cells are also being examined. The functional aspects under investigation are: proliferation of lymphocytes, enterocytes and tumor cells and insulin secretion by pancreatic islets. The activity and expression of key enzymes of the mestabolism of glucose (hexokinase, glucose-6-phosphate dehydrogenase and citrate synthase) and glutamine (phosphate-dependent glutaminase) and of the antioxidant enzymes (Cu/Zn- and Mn-superoxide dismutase, catalase and glutathione peroxidase) are being examined. The experiments performed present evidence that cholesterol might regulate the gene expression of catalase. Briefly, our hypothesis is that lipids produced and exported by circulating monocytes/macrophages might regulate the metabolism of several cell types and their function. A confirmation of this proposition will certainly have implications for understanding and therapies of several pathologies such as immunodeficiencies, neoplasias and diabetes. (AU)