Propofol treatment inhibits constitutive apoptosis in human primary neutrophils and granulocyte-differentiated human HL60 cells

Chung-Hsi Hsing, Chia-Ling Chen, Wei-Chieh Lin, Chiou-Feng Lin

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article numbere0129693
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 10 2015

Fingerprint

Glycogen Synthase Kinase 3
HL-60 Cells
Propofol
granulocytes
Granulocytes
neutrophils
Neutrophils
apoptosis
Apoptosis
Phosphatidylinositol 3-Kinase
phosphatidylinositol 3-kinase
leukemia
inactivation
cells
Myeloid Leukemia
Myeloid Cells
Chemical activation
overdose
retinoic acid
caspase-3

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Propofol treatment inhibits constitutive apoptosis in human primary neutrophils and granulocyte-differentiated human HL60 cells. / Hsing, Chung-Hsi; Chen, Chia-Ling; Lin, Wei-Chieh; Lin, Chiou-Feng.

In: PLoS One, Vol. 10, No. 6, e0129693, 10.06.2015.

Research output: Contribution to journalArticle

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