Apoptosis is associated with an increase in saturated fatty acid containing phospholipids in the neuronal cell line, HN2-5.

Two widely different paradigms of stress, hypoxia and nutrient deprivation, were observed to trigger apoptosis in a clonal neuronal (hippocampal) cell line (HN2-5) as judged by DNA laddering analysis and chromatin condensation. Since according to its original definition, apoptosis is concomitant with a dramatic change in cell morphology, the composition of major phospholipids that determine morphological properties of cells was analyzed in this study. We observed a significant increase (10-20%) in the proportion of saturated fatty acid side chains only in phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI) but not in phosphatidylcholine (PC). This increase was independent of the paradigm of stress used (hypoxia or nutrient deprivation) to initiate apoptosis. Since phospholipids constitute the fabric of both plasma membranes as well as the membranes surrounding the intracellular organelles such as the lysosomes, endoplasmic reticulum and the nuclei, such an apoptosis-associated, selective change in phospholipid composition could cause a dramatic and overall change in membrane fluidity, thus producing the typical shrinking, deformation and porosity of both nuclear as well as plasma and lysosomal membranes as observed in apoptotic cells. Leakiness of lysosomal and nuclear membranes could cause diffusion of deoxyribonucleases into cell nuclei, thus resulting in the characteristic cleavage and laddering of chromosomal DNA which accompany apoptosis.