Anesthetic propofol causes glycogen synthase kinase-3β-regulated lysosomal/mitochondrial apoptosis in macrophages

Anesthesiology
Chung-Hsi HsingChiou-Feng Lin

Abstract

Overdose propofol treatment with a prolong time causes injury to multiple cell types; however, its molecular mechanisms remain unclear. Activation of glycogen synthase kinase (GSK)-3β is proapoptotic under death stimuli. The authors therefore hypothesize that propofol overdose induces macrophage apoptosis through GSK-3β. Phagocytic analysis by uptake of Staphylococcus aureus showed the effects of propofol overdose on murine macrophages RAW264.7 and BV2 and primary human neutrophils in vitro. The authors further investigated cell apoptosis in vitro and in vivo, lysosomal membrane permeabilization, and the loss of mitochondrial transmembrane potential (MTP) by propidium iodide, annexin V, acridine orange, and rhodamine 123 staining, respectively. Protein analysis identified activation of apoptotic signals, and pharmacologic inhibition and genetic knockdown using lentiviral-based short hairpin RNA were further used to clarify their roles. A high dose of propofol caused phagocytic inhibition and apoptosis in vitro for 24 h (25 μg/ml, in triplicate) and in vivo for 6 h (10 mg/kg/h, n = 5 for each group). Propofol induced lysosomal membrane permeabilization and MTP loss while stabilizing MTP and inhibiting caspase protected cells fro...Continue Reading

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Citations

Sep 18, 2012·Apoptosis : an International Journal on Programmed Cell Death·Shu-Yu LiuChiou-Feng Lin
May 30, 2015·International Journal of Molecular Sciences·Ming-Chung LinChung-Hsi Hsing
Jan 1, 2013·Biochemical and Biophysical Research Communications·Yoshikazu YasudaJ A Jeevendra Martyn
Jan 16, 2013·Toxicology and Applied Pharmacology·Ming-Chung LinChiou-Feng Lin
Mar 25, 2015·Journal of Cardiothoracic and Vascular Anesthesia·Christopher Lotz, Franz Kehl
Jul 13, 2013·Anesthesiology·Angela K SaetteleDavid J Murray
Jun 10, 2016·Scientific Reports·Tsung-Ting TsaiChiou-Feng Lin
Dec 31, 2017·Journal of Anesthesia·Koji KidoTokujiro Uchida
Dec 14, 2018·Experimental and Therapeutic Medicine·Long ZhouYuantao Li
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Dec 25, 2015·World Journal of Emergency Medicine·Jun-Ping ChenShi-Hai Zhang
Jan 11, 2021·Journal of Neuroinflammation·Xiaoying CaiZhongxing Wang
Apr 8, 2020·Free Radical Biology & Medicine·Pandian NagakannanEftekhar Eftekharpour

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