title: Investigation of 2,6-diisopropylphenol (propofol)-evoked Ca2+ movement and cell death in human glioblastoma cells.
abstract: This study examined whether propofol altered [Ca(2+)](i) and caused cell death in DBTRG-05MG cells. Propofol at 400-1000μM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was decreased partially by removal of extracellular Ca(2+). Propofol-induced Ca(2+) influx was not altered by nifedipine, econazole, SK&F96365, and protein kinase C (PKC) activators; but was inhibited by PKC inhibitor. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished propofol-induced [Ca(2+)](i) rise. Incubation with propofol inhibited thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C (PLC) with U73122 abolished propofol-induced [Ca(2+)](i) rise. At 300-700μM, propofol killed cells in a concentration-dependent manner. The cytotoxic effect of propofol was partly reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/PI staining further showed that 300-500μM propofol evoked apoptosis. Propofol also increased reactive oxygen species (ROS) production. Overall, propofol induced a [Ca(2+)](i) rise by inducing PLC- and PKC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via non store-operated Ca(2+) channels. Propofol induced cell death that might involve ROS-mediated apoptosis.
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Lu
mesh_terms: D018686:Anesthetics, Intravenous / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005909:Glioblastoma; D006801:Humans; D015742:Propofol / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D017382:Reactive Oxygen Species; D010738:Type C Phospholipases; D002118:Calcium; D015742:Propofol