Stimulation of Lipid Synthesis in Reticulocytes as a Response to Membrane Damage

Exposure of rabbit reticulocytes to agents which damage the cell membrane by a variety of different mechanisms stimulates the incorporation of radioactive acetate and glycerol into membrane lipids. An increase in the rate of lipid synthesis occurs within minutes at 37°C at concentrations of the agents which do not cause spontaneous cell lysis. Different agents do not increase synthesis of different classes of reticulocyte lipids to the same extent. 1.5 x 10^-4M vincristine stimulates the incorporation of precursors only into neutral lipids while, in contrast, 10^-3M puromycin stimulates only synthesis of the three carbon backbone of phospholipids. The effects of these two agents are additive, confirming their selective action on distinct pathways. The effect of puromycin is independent of its ability to inhibit protein synthesis. 3.6 x 10^-3M butanol stimulates pathways for synthesis of both neutral lipids and phospholipids to approximately equal extents. The major effect of 4% hydrogen peroxide is to increase exchange of labeled fatty acids, but it also increases phopholipid synthesis. The evidence indicates that a metabolic response of the reticulocyte to membrane damage is to increase synthesis of neutral lipid and phospholipid, and the particular pathway or pathways which respond are related to the agent used to induce damage.