title: Apoptosis is associated with an inhibition of aminophospholipid translocase (APTL) in CNS-derived HN2-5 and HOG cells and phosphatidylserine is a recognition molecule in microglial uptake of the apoptotic HN2-5 cells.
abstract: A balance of the activities of multiple enzymes maintains the typical asymmetry of plasma membrane lipids in healthy cells. Such enzyme activities are (a) the aminophopholipid translocase (APTL) (a lipid-selective P-type ATPase that catalyzes inward movement of aminophospholipids), (b) the scramblase (a calcium-dependent and ATP-independent enzyme that catalyzes both inward and outward movement of lipids), (c) the floppase (an ATP-dependent enzyme that catalyzes only outward movement of lipids). Activation or inhibition of any one of these enzymes would lead to a loss in this asymmetry. Apoptosis-associated externalization of phophatidylserine has been reported for many different cell-types, but the exact mechanism involved in this loss of membrane asymmetry has not been identified yet. In this report we demonstrate concurrence of APTL inhibition, caspase-3 activation and apoptosis in CNS-derived HN2-5 and HOG cells. Additionally, we provide data to demonstrate that the phagocytosis of apoptotic, CNS-derived HN2-5 cells by the microglial cells requires recognition through phosphatidylserine (PS). Thus the enzyme aminopholipid translocase is inhibited during apoptosis of CNS-derived cells and this alone could account for the loss of plasma membrane lipid-asymmetry observed in these cells.
authors.affiliation: Department of Chemistry and CSI/IBR, Center for Developmental Neuroscience and Developmental Disabilities, City University of New York, The College of Staten Island, Building 6S, Room 326, 2800 Victory Boulevard, Staten Island, NY 10314, USA.
authors.forename: Paramita
authors.initials: P
authors.lastname: Das
authors.forename: Rima
authors.initials: R
authors.lastname: Estephan
authors.forename: Probal
authors.initials: P
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D015687:Cell Hypoxia / Q000502:physiology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism* / Q000494:pharmacology; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases