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Alterations in reactive oxygen, pH, and calcium in astrocytoma cells during lethal injury.

Abstract
Exposure of cultured human astrocytoma cells to iodoacetic acid results in rapid depletion of cellular ATP and cell death. Pathophysiological changes in the injured cells, including formation of reactive oxygen species (ROS), cell viability, glutathione, pH, and cytosolic calcium, were characterized at the cellular level via fluorescence microscopy. After iodoacetic acid treatment, cellular ATP and intracellular glutathione fell sharply to undetectable levels within 2 h. ROS, as detected by the oxidation of dichlorofluorescein, appeared in 20 min and reached a maximum before the loss of membrane integrity. Cells became acidotic within 10 min. Cytosolic free calcium concentration exhibited a slow increase and then a sharp influx shortly before the rupture of the cell membrane. The addition of lipophilic antioxidants, nordihydroguaiaretic acid or the troloxamine U-78517F, eliminated the accumulation of ROS and delayed the onset of cell death without affecting other parameters observed in the early phase of the injury. We conclude that ROS is formed and may play important roles during lethal cell injury caused by energy depletion.
AuthorsY Wu, B M Taylor, F F Sun
JournalThe American journal of physiology (Am J Physiol) Vol. 270 Issue 1 Pt 1 Pg. C115-24 (Jan 1996) ISSN: 0002-9513 [Print] United States
PMID8772436 (Publication Type: Journal Article)
Chemical References
  • Iodoacetates
  • Reactive Oxygen Species
  • Hydrogen
  • Adenosine Triphosphate
  • Glutathione
  • Calcium
  • Iodoacetic Acid
Topics
  • Adenosine Triphosphate (antagonists & inhibitors, metabolism)
  • Animals
  • Astrocytoma (metabolism, pathology, physiopathology)
  • Calcium (metabolism)
  • Cell Death
  • Cell Membrane Permeability (drug effects)
  • Cricetinae
  • Cytosol (metabolism)
  • Glutathione (metabolism)
  • Humans
  • Hydrogen (metabolism)
  • Hydrogen-Ion Concentration
  • Iodoacetates (pharmacology)
  • Iodoacetic Acid
  • Reactive Oxygen Species (metabolism)
  • Tumor Cells, Cultured

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