Phospholipase A2-derived lysophosphatidylcholine triggers Ca2+ entry in dystrophic skeletal muscle fibers.
2010
Abstract Duchenne muscular dystrophy is an inherited disease caused by the absence of dystrophin, a structural protein normally located under the sarcolemma of skeletal muscle fibers. Muscle degeneration occurring in this disease is thought to be partly caused by increased Ca 2+ entry through sarcolemmal cationic channels. Using the Mn 2+ quench method, we show here that Mn 2+ entry triggered by Ca 2+ store depletion but not basal Mn 2+ entry relies on Ca 2+ -independent PLA 2 (iPLA 2 ) activity in dystrophic fibers isolated from a murine model of Duchenne muscular dystrophy, the mdx 5cv mouse. iPLA 2 was found to be localized in the vicinity of the sarcolemma and consistently, the iPLA 2 lipid product lysophosphatidylcholine was found to trigger Ca 2+ entry through sarcolemmal channels, suggesting that it acts as an intracellular messenger responsible for store-operated channels opening in dystrophic fibers. Our results suggest that inhibition of iPLA 2 and lysophospholipid production may be of interest to reduce Ca 2+ entry and subsequent degeneration of dystrophic muscle.
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