Level of cytosolic free calcium during acetaminophen toxicity in mouse hepatocytes

A.W. Harman, S.D. Mahar, P.C. Burcham, Barry Madsen

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cytosolic free calcium was calculated from the ratio of emitted fluorescence at > 475 nm produced by excitation at 340 and 380 nm, using a double-intensified silicon target camera and digital image processing. In the presence of 5 mM acetaminophen, cell death did not occur for 2 hr, but the toxic lesion that ultimately killed the cells occurred as early as 1 hr. If cytosolic free calcium plays an important role in these toxic events, it would be expected to increase during this period. However, during a 2-hr exposure, cytosolic free calcium concentration in cells exposed to acetaminophen was not different from control. In hepatocytes incubated for longer than 2 hr, the calcium concentration increased shortly before loss of cell viability (i.e., as a late event), consistent with an influx of calcium through a damaged cell membrane. This late increase in calcium occurred well after the appearance of cell surface blebs. The data suggest that there is no sustained change in cytosolic free calcium in acetaminophen injury either before or during the time when irreversible toxic events occur in hepatocytes.
    Original languageEnglish
    Pages (from-to)665-670
    JournalMolecular Pharmacology
    Volume41
    Publication statusPublished - 1992

    Fingerprint

    Acetaminophen
    Hepatocytes
    Calcium
    Poisons
    Cell Death
    Fura-2
    Silicon
    Blister
    Fluorescence Microscopy
    Cell Survival
    Fluorescence
    Cell Membrane
    Wounds and Injuries

    Cite this

    Harman, A. W., Mahar, S. D., Burcham, P. C., & Madsen, B. (1992). Level of cytosolic free calcium during acetaminophen toxicity in mouse hepatocytes. Molecular Pharmacology, 41, 665-670.
    Harman, A.W. ; Mahar, S.D. ; Burcham, P.C. ; Madsen, Barry. / Level of cytosolic free calcium during acetaminophen toxicity in mouse hepatocytes. In: Molecular Pharmacology. 1992 ; Vol. 41. pp. 665-670.
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    abstract = "It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cytosolic free calcium was calculated from the ratio of emitted fluorescence at > 475 nm produced by excitation at 340 and 380 nm, using a double-intensified silicon target camera and digital image processing. In the presence of 5 mM acetaminophen, cell death did not occur for 2 hr, but the toxic lesion that ultimately killed the cells occurred as early as 1 hr. If cytosolic free calcium plays an important role in these toxic events, it would be expected to increase during this period. However, during a 2-hr exposure, cytosolic free calcium concentration in cells exposed to acetaminophen was not different from control. In hepatocytes incubated for longer than 2 hr, the calcium concentration increased shortly before loss of cell viability (i.e., as a late event), consistent with an influx of calcium through a damaged cell membrane. This late increase in calcium occurred well after the appearance of cell surface blebs. The data suggest that there is no sustained change in cytosolic free calcium in acetaminophen injury either before or during the time when irreversible toxic events occur in hepatocytes.",
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    Harman, AW, Mahar, SD, Burcham, PC & Madsen, B 1992, 'Level of cytosolic free calcium during acetaminophen toxicity in mouse hepatocytes' Molecular Pharmacology, vol. 41, pp. 665-670.

    Level of cytosolic free calcium during acetaminophen toxicity in mouse hepatocytes. / Harman, A.W.; Mahar, S.D.; Burcham, P.C.; Madsen, Barry.

    In: Molecular Pharmacology, Vol. 41, 1992, p. 665-670.

    Research output: Contribution to journalArticle

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    AB - It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cytosolic free calcium was calculated from the ratio of emitted fluorescence at > 475 nm produced by excitation at 340 and 380 nm, using a double-intensified silicon target camera and digital image processing. In the presence of 5 mM acetaminophen, cell death did not occur for 2 hr, but the toxic lesion that ultimately killed the cells occurred as early as 1 hr. If cytosolic free calcium plays an important role in these toxic events, it would be expected to increase during this period. However, during a 2-hr exposure, cytosolic free calcium concentration in cells exposed to acetaminophen was not different from control. In hepatocytes incubated for longer than 2 hr, the calcium concentration increased shortly before loss of cell viability (i.e., as a late event), consistent with an influx of calcium through a damaged cell membrane. This late increase in calcium occurred well after the appearance of cell surface blebs. The data suggest that there is no sustained change in cytosolic free calcium in acetaminophen injury either before or during the time when irreversible toxic events occur in hepatocytes.

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