Oxidized Lipids Control Lipid Order and Phospholipase A2 Activity in Model Membranes

Abstract

Oxidative stress is an important etiologic factor in the pathogenesis of various diseases. The formation of oxidized phospholipid species in vivo induces membrane remodelling with direct pathological implications with a prominent inflammatory component. Secretory phospholipases A2 (sPLA2) are involved in the regulation of inflammation and immune response. Their activity is highly dependent on the lipid membrane composition, structure and organization. In this work, we studied the impact of oxidized phosphatidylcholines (OxPCs) on the membrane lipid order and the sPLA2 activity. The effects of two of the most physiologically active OxPCs, 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero- 3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3- phosphocholine (PGPC) were compared using 1-palmitoyl-2-oleoyl-sn-glycero- 3-phosphocholine (POPC) vesicles. Both OxPCs reduce the membrane lipid order and sPLA2 activity at physiological temperature. Moreover, these changes depend on the chemical nature of the oxidized chains.