Oxy-lipidomics analysis of the oxidation effects of plasmalogens on lipid remodeling of cells under oxidative stress

• Grant number: 17/16140-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): November 01, 2017
• Effective date (End): January 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Sayuri Miyamoto
• Grantee: Rodrigo Lucas de Faria
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Plasmalogens represent approximately 20% of all phospholipids in human cell membranes. Plasmalogens are phospholipids in which the two side-chains are connected to the glycerol backbone via a vinyl ether linkage at the sn-1 position, and an ester linkage, mostly to Polyunsaturated Fatty Acids (PUFAs), at sn-2 position. Although studies have demonstrated the protective effects of plasmalogens in cellular models submitted to oxidative stress, the protective roles of plasmalogens against oxidative stress remain contradictory, e.g, the reaction of plasmalogen with Reactive Oxygen Species (ROS) produces species, which can induce propagation of oxidative damages such as dioxetanes and aldehydes. Previous laboratory experiments have shown that cultured keratinocytes under induced UVA-stress leads to lipid remodeling followed by a substantial decrease in membrane PUFAs and an increase in triacylglycerols enriched in PUFAs (unpublished data). Based on these data and on Bailey's paper (Cell 2015,163:340), in which it was evidenced an antioxidant mechanism involving reallocation of PUFA from membranes to lipids droplets we hypothesized that plasmalogens may play an important role directly or indirectly, as a source of PUFAs in lipids droplets or as source of signalling species (e.g. oxidized lipids) capable to modulate this process. In order to test this hypothesis, the present project has the following aims: a) perform qualitative and quantitative oxy-lipidomics analysis (lipidomics of oxidized and non-oxidized lipids) focused on lipid remodeling induced by UVA stress in two cell lines (HaCat and RPE); b) characterize the main oxidized products (dioxetanes, aldehydes, lysophospholipids, etc.) derived from the reaction of plasmalogen with reactive species generated by UVA stress; C) investigate membrane's PUFAs reallocation to triacylglycerols using DHA labeled with carbon-13. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FARIA, Rodrigo Lucas de. Deleterious effects of phosphatidylethanolamine plasmalogen oxidation via singlet molecular oxygen. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.