Toxic injury from mercuric chloride in rat hepatocytes

Anna Liisa Nieminen, Gregory James Gores, Thomas L. Dawson, Brian Herman, John J. Lemasters

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Abstract

The relationship between cytosolic free Ca2+, mitochondrial membrane potential, ATP depletion, pyridine nucleotide fluorescence, cell surface blebbing, and cell death was evaluated in rat hepatocytes exposed to HgCl2. In cell suspensions, 50 μM HgCl2 oxidized pyridine nucleotides between 1/2 and 2 min, caused ATP depletion between 2 and 5 min, and produced an 89% loss of cell viability after 20 min. Rates of cell killing were identical in high (1.2 mM) and low (2.6 μM) Ca2+ buffers. Cytosolic free Ca2+ was determined in 1-day cultured hepatocytes by ratio imaging of Fura-2 employing multiparameter digitized video microscopy. In high Ca2+ medium, HgCl2 caused a 3-4-fold increase of free Ca2+ beginning after 6-7 min, but free Ca2+ did not change in low Ca2+ medium. Bleb formation occurred after about 4-5 min in both buffers prior to any increase of free Ca2+. Subsequently, in high Ca2+ medium, blebs became hot spots of free Ca2+ (>600 nM). After about 2 min of exposure to HgCl2, rhodamine 123 fluorescence redistributed from mitochondrial to cytosolic compartments signifying collapse of the mitochondrial membrane potential. The results taken together demonstrate that bleb formation, ATP depletion, and the onset of cell death are not dependent on an increase of cytosolic free Ca2+. HgCl2 toxicity appears to be a consequence of inhibition of oxidative phosphorylation leading to ATP depletion and cell death.

Original languageEnglish (US)
Pages (from-to)2399-2408
Number of pages10
JournalJournal of Biological Chemistry
Volume265
Issue number4
StatePublished - Feb 5 1990

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Nieminen, A. L., Gores, G. J., Dawson, T. L., Herman, B., & Lemasters, J. J. (1990). Toxic injury from mercuric chloride in rat hepatocytes. Journal of Biological Chemistry, 265(4), 2399-2408.