ELSEVIER Biochimica et Biophysica Acta 1304 (1996) 171-178 BIOCHIMICA ET BIOPHYSICAACI'A BBN Rapid report Apoptosis is associated with an increase in saturated fatty acid containing phospholipids in the neuronal cell line, HN2-5 Jyoti K. Singh a, Amitava Dasgupta b, Tatyana Adayev a S. Akhtar Shahmehdi a, David Hammond c, Probal Banerjee a,* a Department of Chemistry and CSI/IBR Center for Developmental Neuroscience, The College of Staten Island/CUNY, Staten Island, NY 10314, USA b Pathology and Biochemistry, University of New Mexico Hospital, Albuquerque, NM 87102, USA c The Nemour's Children's Clinic and Mayn Medical School, Jacksonville, FL 32207, USA Received 19 August 1996; accepted 27 August 1996 Abstract 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), phos- phatidylserine (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. Keywords: Apoptosis; Saturated fatty acid containing phospholipid; Membrane lipid composition Apoptosis is one of the two major mechanisms (apoptosis and necrosis) by which cells die. Unlike necrosis, which is a passive process, apoptosis is an active process, requiring RNA and protein synthesis. However, apoptosis has been so far defined only in morphological terms [ 1 ]. In necrosis cellular swelling, * Corresponding author. Fax: +1 (718) 9823944; E-mail: banerjee@postbox.csi.cuny.edu membrane rupture and bursting are observed, whereas in apoptosis the cells shrink and apparently intact membranes appear ruffled and bubbled (zeiosis), probably consequent to disruption of the cytoskeleton and resultant shifting of membrane anchorage. Since lipids or mainly phospholipids, form the membrane structure, regulate its fluidity and thus prepare the bilayer for the cradling and maintenance of active membrane proteins, any gross change in membrane structure, such as that observed during apoptosis, is 0005-2760/96/$15.00 Copyright © 1996 Elsevier Science All rights reserved. PI1 S0005-2760(96)00134-8