title: Propofol Treatment Inhibits Constitutive Apoptosis in Human Primary Neutrophils and Granulocyte-Differentiated Human HL60 Cells.
abstract: Apoptosis regulation is essential for neutrophil homeostasis. We previously demonstrated that a process involving glycogen synthase kinase (GSK)-3β determines neutrophil apoptosis. As for this apoptotic process, an overdose of propofol (2,6-Diisopropylphenol; 25 μg/ml or 140 μM) also causes GSK-3β-mediated macrophage apoptosis; however, the early deactivation of GSK-3β with low-dose propofol has been shown. Therefore, we hypothesize that low-dose propofol may induce neutrophil survival via GSK-3β inactivation. Following in vitro culture, the therapeutic concentration of propofol (10 μg/ml or 56 μM) treatment decreased constitutive apoptosis in isolated human primary neutrophils and in granulocyte-differentiated HL60 cells after all-trans retinoic acid (1 μM) treatment. The inactivation of phosphatidylinositol 3-kinase (PI3-kinase)/AKT and the activation of GSK-3β results in myeloid cell leukemia 1 (Mcl-1) down-regulation, the loss of the mitochondrial transmembrane potential, and caspase-3 activation in these cells, which is accompanied by apoptosis. Notably, propofol treatment attenuates these effects in a PI3-kinase-regulated manner. We found that propofol initiates PI3-kinase/AKT-mediated GSK-3β inactivation and Mcl-1 stabilization, rescuing the constitutive apoptosis in primary neutrophils and granulocyte-differentiated acute promyelocytic leukemia HL60 cells.
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.affiliation: Translational Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
mesh_terms: D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015742:Propofol / Q000009:adverse effects / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D015742:Propofol