Lipid peroxidation is essential for phospholipase C activity and the inositol-trisphosphate-related Ca2+ signal

A.-M. Domijan, S. Kovac, A. Y. Abramov
2013 Journal of Cell Science  
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 has been implicated in a number of neurological diseases; however, antioxidant therapies targeting brain diseases have been unsuccessful. Such failure might be related to inhibition of ROSinduced signalling in the brain. Using direct kinetic measures of lipid peroxidation in astrocytes and measurements of lipid
more » ... of lipid peroxidation products in brain tissue, we here show that phospholipase C (PLC) preferentially cleaves oxidised lipids. Because of this, an increase in the rate of lipid peroxidation leads to increased Ca 2+ release from endoplasmic reticulum (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 Ca 2+ signalling. This implies that antioxidants can compromise intracellular Ca 2+ signalling through inhibition of PLC, and that PLC plays a dual role -signalling and antioxidant defence.
doi:10.1242/jcs.138370 pmid:24198393 fatcat:x3ljocpponcn3ejwogpmj5akva