Lntracellular Ca2+ and cytotoxicity

William S. Lynn, Darren Mathews, Miles Cloyd, James C. Wallwork, Aubrey Thompson, Clifford Sachs

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Following injury or activation in some immune cell lines, elevation of intracellular Caz+ concentration (Cap) is an early and major event that precedes cell death. Agents shown to elevate Ca:’ and to result subsequently in the death of some cells include human immunodeficiency virus (HIW (in T,+ cells), 2Ihydroxy cholesterol, tumor necrosis factor (TNF), cyclosporine, dexamethasone, a-interferon, and Ca" ionophores. The effects of these agents, both on Car and on cytotoxicity, are additive. This type of Ca"-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 Cap (e.g., phorbol esters, diglycerides, lipoproteins [LDL], oleic acid, or serum) under appropriate conditions ameliorate the Caz+-inducedc ytotoxicity.’J Metabolism of other divalent metals, i.e., Zn’+ and Cd", also become altered with cell injury, e.g., glucocorticoids elevate Car, but block uptake of Znz’. These observations support the idea that chronic elevation of Cat* 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 Zn".

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

ASJC Scopus subject areas

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

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