期刊
JOURNAL OF CELL SCIENCE
卷 127, 期 1, 页码 21-26出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.138370
关键词
Ca2+; Lipid peroxidation; Phospholipase C; Astrocyte
类别
资金
- Liverhulme Trust
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 ROS-induced signalling in the brain. Using direct kinetic measures of lipid peroxidation in astrocytes and measurements 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 Ca2+ 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 Ca2+ signalling. This implies that antioxidants can compromise intracellular Ca2+ signalling through inhibition of PLC, and that PLC plays a dual role - signalling and antioxidant defence.
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