Enhanced lysosomal phospholipid degradation and lysophospholipid production due to free radicals

To pursue the hypothesis that peroxidized lipids may become preferred substrates for endogenous phospholipases, we injured hepatic lysosomes by adding an exogenous free radical generating system [dihydroxyfumurate + Fe3+-ADP]; this system rapidly lysed hepatic lysosomes at pH 6.0, with maximal changes at 30 min. The production of malondialdehyde [MDA] plateaued rapidly. At 20 min the degradation of phosphatidylethanolamine [PE] was greater than phosphatidylcholine [PC]: 52% and 17%, respectively. Sphingomyelin and neutral lipids did not decrease. Most interesting was the significant increase of lysoPC [329%; p less than 0.05] at 10 min and [381%; p less than 0.01] after 20 min of incubation; lysoPE production became significant [766%; p less than 0.05] at 20 min. This enhanced production of lysoPC and lysoPE suggests a new mechanism to increase the production of amphiphilic lipids during ischemia, that is active at moderately acid pH without added calcium.