Intracellular Ca²⁺and Cytotoxicity

Abstract

Following injury or activation in some immune cell lines, elevation of intracellular Ca2+ concentration (Cai2+) is an early and major event that precedes cell death. Agents shown to elevate Cai2+ 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, alpha-interferon, and Ca2+ ionophores. The effects of these agents, both on Cai2+ 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 Cai2+ (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 Cai2+, but block uptake of Zn2+. These observations support the idea that chronic elevation of Cai2+ 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+.

Analysis of differently expressed proteins and transcripts in gills of Penaeus vannamei after yellow head virus infection

“…SCPs normally bind to Ca 21 ions and function as a cytosolic Ca 21 buffer [27], and their down-regulation may impair Ca 21 binding. This might lead to the activation of phospholipase, protease, and endonuclease, which could damage or destroy the YHVinfected cells [28][29][30].…”

Quadruply Stranded Metallo-Supramolecular Helicate [Pd2(hextrz)4]4+ Acts as a Molecular Mimic of Cytolytic Peptides

“… These comparisons suggested that the nuclear condensation caused by the helicate was due to an influx of extracellular Ca 2+ . This was confirmed by fluo-4 labeling which displayed a sharp spike for Ca 2+ uptake following helicate exposure resembling the Ca 2+ uptake profile of cells treated with A23187 . However, the characteristics of [Pd 2 (hextrz) 4 ] 4+ induced cell death were distinct from both ionophore and detergent, prompting us to consider that the helicate likely caused pore formation.…”

“…This was confirmed by fluo-4 labeling which displayed a sharp spike for Ca 2+ uptake following helicate exposure resembling the Ca 2+ uptake profile of cells treated with A23187. 60 However, the characteristics of [Pd 2 (hextrz) 4 ] 4+ induced cell death were distinct from both ionophore and detergent, prompting us to consider that the helicate likely caused pore formation. This was supported by DiI measurements which showed that structural changes occurred rapidly in the plasma membrane following [Pd 2 (hextrz) 4 ] 4+ addition (Figure 6).…”