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Effects of propofol on intracellular Ca2+ homeostasis in human astrocytoma cells.

Abstract

The effects of propofol, a short-acting general anesthetic, upon cell growth and Ca(2+) signaling in a human astrocytic cell line were examined. Exposure of cells to graded concentrations of propofol resulted in a dose-dependent decrease in cell number with an inhibitory concentration of cell viability (IC50) of 31.7+/-1.2 microM. To evaluate the changes in intracellular Ca(2+) homeostasis induced by propofol, cytoplasmic and mitochondrial Ca(2+) were measured by fluorescence imaging. Mitochondrial Ca(2+) increased while cytoplasmic Ca(2+) decreased significantly at a propofol concentration lower than the IC50 (10 microM for 24 h, 1 microM for 72 h). In addition, propofol diminished the Ca(2+) response induced by fetal bovine serum (FBS). To determine the source of Ca(2+) alterations induced by propofol, pharmacologic agents targeting intracellular Ca(2+) homeostasis mechanisms were used. Nifedipine, an L-type Ca(2+) channel blocker, decreased FBS-induced Ca(2+) response of control cells to a level similar to propofol treated cells. However, diazoxide (a K(+)-ATP channel opener) administered 1 h before FBS addition restored the FBS response in propofol treated cells to a level similar to control. In addition, diazoxide increased mitochondrial Ca(2+) in control cells to a level comparable to propofol treated cells suggesting activation of these channels by propofol treatment. Addition of 1 muM RU-360 (a selective blocker of the mitochondrial Ca(2+) uniporter) for 30 min prior to propofol treatment restored mitochondrial and cytoplasmic Ca(2+) to control levels. These data suggest that voltage operated Ca(2+) channels, mitochondrial Ca(2+) and K(+)-ATP channels may be targets of propofol action in astrocytes.

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  • Authors+Show Affiliations

    ,

    Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843-4458, USA. rmouneimne@cvm.tamu.edu

    , ,

    Source

    Brain research 1145: 2007 May 11 pg 11-8

    MeSH

    Anesthetics, Intravenous
    Astrocytes
    Brain
    Calcium
    Calcium Channel Agonists
    Calcium Channel Blockers
    Calcium Channels
    Calcium Signaling
    Cell Death
    Cell Line, Tumor
    Cytosol
    Dose-Response Relationship, Drug
    Homeostasis
    Humans
    Intracellular Fluid
    Mitochondria
    Potassium Channels
    Propofol

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17328872

    Citation

    Barhoumi, Rola, et al. "Effects of Propofol On Intracellular Ca2+ Homeostasis in Human Astrocytoma Cells." Brain Research, vol. 1145, 2007, pp. 11-8.
    Barhoumi R, Burghardt RC, Qian Y, et al. Effects of propofol on intracellular Ca2+ homeostasis in human astrocytoma cells. Brain Res. 2007;1145:11-8.
    Barhoumi, R., Burghardt, R. C., Qian, Y., & Tiffany-Castiglioni, E. (2007). Effects of propofol on intracellular Ca2+ homeostasis in human astrocytoma cells. Brain Research, 1145, pp. 11-8.
    Barhoumi R, et al. Effects of Propofol On Intracellular Ca2+ Homeostasis in Human Astrocytoma Cells. Brain Res. 2007 May 11;1145:11-8. PubMed PMID: 17328872.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of propofol on intracellular Ca2+ homeostasis in human astrocytoma cells. AU - Barhoumi,Rola, AU - Burghardt,Robert C, AU - Qian,Yongchang, AU - Tiffany-Castiglioni,Evelyn, Y1 - 2007/02/02/ PY - 2006/11/17/received PY - 2007/01/22/revised PY - 2007/01/26/accepted PY - 2007/3/3/pubmed PY - 2007/6/27/medline PY - 2007/3/3/entrez SP - 11 EP - 8 JF - Brain research JO - Brain Res. VL - 1145 N2 - The effects of propofol, a short-acting general anesthetic, upon cell growth and Ca(2+) signaling in a human astrocytic cell line were examined. Exposure of cells to graded concentrations of propofol resulted in a dose-dependent decrease in cell number with an inhibitory concentration of cell viability (IC50) of 31.7+/-1.2 microM. To evaluate the changes in intracellular Ca(2+) homeostasis induced by propofol, cytoplasmic and mitochondrial Ca(2+) were measured by fluorescence imaging. Mitochondrial Ca(2+) increased while cytoplasmic Ca(2+) decreased significantly at a propofol concentration lower than the IC50 (10 microM for 24 h, 1 microM for 72 h). In addition, propofol diminished the Ca(2+) response induced by fetal bovine serum (FBS). To determine the source of Ca(2+) alterations induced by propofol, pharmacologic agents targeting intracellular Ca(2+) homeostasis mechanisms were used. Nifedipine, an L-type Ca(2+) channel blocker, decreased FBS-induced Ca(2+) response of control cells to a level similar to propofol treated cells. However, diazoxide (a K(+)-ATP channel opener) administered 1 h before FBS addition restored the FBS response in propofol treated cells to a level similar to control. In addition, diazoxide increased mitochondrial Ca(2+) in control cells to a level comparable to propofol treated cells suggesting activation of these channels by propofol treatment. Addition of 1 muM RU-360 (a selective blocker of the mitochondrial Ca(2+) uniporter) for 30 min prior to propofol treatment restored mitochondrial and cytoplasmic Ca(2+) to control levels. These data suggest that voltage operated Ca(2+) channels, mitochondrial Ca(2+) and K(+)-ATP channels may be targets of propofol action in astrocytes. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/17328872/Effects_of_propofol_on_intracellular_Ca2+_homeostasis_in_human_astrocytoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(07)00273-9 DB - PRIME DP - Unbound Medicine ER -