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.
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.
Das
Paramita
P
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.
Estephan
Rima
R
Banerjee
Probal
P
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
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