Calcium-Dependent Mechanisms in Drug Toxicity and Cell Killing View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

1995

AUTHORS

Giorgio Bellomo , Ernesto Carafoli , Claus W. Heizmann , Alan Horton , Sten Orrenius

ABSTRACT

There is now convincing evidence that the calcium ion plays a critical role in cytotoxicity and cell death. In a variety of experimental models cell killing has been found to be preceded by intracellular Ca2+ accumulation, and pretreatment with Ca2+ entry blockers or intracellular Ca2+ chelators has been shown to provide protection. Further, resistance to cell killing has been reported to correlate with cellular levels of the Ca2+-binding protein calbindin-D28k in neurons and thymoma cells. It is also clear that sustained increases in intracellular Ca2+ level can activate cytotoxic mechanisms which result in perturbations of cell structure and function. For example, the stimulation of Ca2+-dependent proteases can cause a disruption of cytoskeletal organization, and Ca2+-mediated phospholipase activation can result in an impairment of mitochondrial function and cessation of ATP synthesis. The activation of Ca2+, Mg2+-dependent endonuclease(s) is associated with characteristic chromatin cleavage which is a hallmark of apoptotic cell killing in the immune system and other tissues. The aim of this overview is to discuss some recent advances in our knowledge of the role of the calcium ion in cytotoxicity. More... »

PAGES

453-460

References to SciGraph publications

Book

TITLE

Pharmacological Sciences: Perspectives for Research and Therapy in the Late 1990s

ISBN

978-3-0348-7220-1
978-3-0348-7218-8

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-3-0348-7218-8_46

DOI

http://dx.doi.org/10.1007/978-3-0348-7218-8_46

DIMENSIONS

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