Cell death mechanisms and their implications in toxicology

Necrotic cell death was long regarded as the ultimate consequence of chemical toxicity and was thought to result from simple cell failure because of toxic interference with vital cell functions. Introduction of the novel concept of programmed cell death (PCD), or apoptosis, has changed this view dra...

Full description

Saved in:
Bibliographic Details
Published in:Toxicological sciences 2011-01, Vol.119 (1), p.3-19
Main Authors: Orrenius, Sten, Nicotera, Pierluigi, Zhivotovsky, Boris
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Apoptosis - genetics
Apoptosis - physiology
Autophagy
Calcium Signaling
Cell Death
Humans
Medicin och hälsovetenskap
Phagocytosis
Reactive Oxygen Species - metabolism
Subcellular Fractions - metabolism
Toxicology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Necrotic cell death was long regarded as the ultimate consequence of chemical toxicity and was thought to result from simple cell failure because of toxic interference with vital cell functions. Introduction of the novel concept of programmed cell death (PCD), or apoptosis, has changed this view dramatically. This development has been further stimulated by the characterization of several other genetically PCD modalities, such as autophagy and pyroptosis. Like apoptosis, these modes of cell death are governed by complex signaling networks, containing "switches" responsible for cross talk between them. Recruitment or repression of these cell death signaling networks by foreign chemicals can lead to acute as well as chronic toxicity. In many instances, such effects of toxicants are mediated by disruption/modulation of cellular Ca(2+) homeostasis or increased generation of reactive oxygen species in the mitochondria or other intracellular compartments. Caspases, calpains, lysosomal proteases, and endonucleases are the main executioners of cell death, and they often co-operate during the execution stage of apoptosis. Finally, dead or dying cells are recognized and engulfed by phagocytes to prevent inflammation and associated tissue damage. Defective macrophage engulfment and degradation of cell corpses may also result from toxicity and can contribute to both the inflammatory response and dysregulation of tissue homeostasis. Hence, the cell death and phagocytosis regulatory networks offer a multitude of targets for toxic chemicals.
ISSN:1096-6080
1096-0929
1096-0929
DOI:10.1093/toxsci/kfq268