Intracellular Ca2+ and cytotoxicity

W. S. Lynn, D. Mathews, M. Cloyd, J. C. Wallwork, A. Thompson, C. Sachs

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14 Scopus citations

Abstract

Following injury or activation in some immune cell lines, elevation of intracellular Ca2+ concentration (Ca(i)2+) is an early and major event that precedes cell death. Agents shown to elevate Ca(i)2+ and to result subsequently in the death of some cells include human immunodeficiency virus (HIV) (in T4 + cells), 25-hydroxy cholesterol, tumor necrosis factor (TNF), cyclosporine, dexamethasone, α-interferon, and Ca2+ ionophores. The effects of these agents, both on Ca(i)2+ and on cytotoxicity, are additive. This type of Ca2+-related cytotoxicity may be associated with either accelerated synthesis of triglycerides (TNF), accelerated synthesis of cholesterol ester (25-hydroxy cholesterol), or cholesterol (HIV) and terminally with declining synthesis of structural phospholipid. Agents that can lower Ca(i)2+ (e.g., phorbol esters, diglycerides, lipoproteins [LDL], oleic acid, or serum) under appropriate conditions ameliorate the Ca2+-induced cytotoxicity. Metabolism of other divalent metals, i.e., Zn2+ and Cd2+, also become altered with cell injury, e.g., glucocorticoids elevate Ca(i)2+, but block uptake of Zn2+. These observations support the idea that chronic elevation of Ca(i)2+ by many chemically unrelated agents leads to cell death by creating imbalance both in cell biosynthetic mechanisms - especially in those controlling lipid metabolism - as well as creating imbalances in metabolism of other trace metals, especially Zn2+.

Original languageEnglish (US)
Pages (from-to)323-330
Number of pages8
JournalArchives of Environmental Health
Volume44
Issue number5
StatePublished - 1989

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ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Lynn, W. S., Mathews, D., Cloyd, M., Wallwork, J. C., Thompson, A., & Sachs, C. (1989). Intracellular Ca2+ and cytotoxicity. Archives of Environmental Health, 44(5), 323-330.