Lipid peroxidation is essential for phospholipase C activity and IP3 related calcium signal

Abstract

Reactive oxygen species (ROS) are produced in enzymatic and non-enzymatic reactions and have important roles in cell signalling but also detrimental effects. ROS-induced damage was implicated in a number of neurological diseases; however, antioxidant therapies targeting brain diseases have been unsuccessful. Such failure may be related to inhibition of ROS induced signalling in the brain. Using direct kinetic measures of lipid peroxidation in astrocytes and measurements of lipid peroxidation product in brain tissue, we here show that phospholipase C (PLC) preferentially cleaves oxidised lipids. As a result an increase in the rate of lipid peroxidation leads to increased Ca2+ release from ER-stores in response to physiological activation of purinoreceptors with ATP. Both vitamin E and its water-soluble analogue Trolox, potent ROS scavengers, were able to suppress PLC activity therefore dampening intracellular Ca2+ signalling. This implies that antioxidants may compromise intracellular Ca2+ signalling via inhibition of PLC and that PLC plays a dual role - signalling and antioxidant defence.