Mechanisms of cell death

Abstract

Two distinct morphological patterns of cell death have been recognized, termed necrosis and apoptosis. Apoptosis, or programmed cell death, occurs in both physiological and pathological conditions. It arises due to an elevation of cytosolic free calcium concentration resulting in activation of a nuclear endonuclease. Activated endonuclease produces oligonucleosome-length DNA fragments. This DNA cleavage can directly precipitate cell death. Both glucocorticoids and TCDD may induce apoptosis by production of a heat labile factor that mediates calcium influx whereas tributyltin causes the opening of calcium channels. Evidence that perturbation in calcium homeostasis is an important event in cell necrosis is becoming increasingly persuasive, but the events that propagate the lesion are still unclear. Despite evidence for cytoskeletal disruption, activation of degradative enzymes such as proteases and phospholipase A2 and stimulation of other enzymes such as poly (ADP-ribose) polymerase, the exact role that these play in cell killing is not resolved. Indeed, recently the radical dichotomy between apoptosis and necrotic cell death has come into question. It is clear that further work is required to determine the role played by some elements of the apoptotic process in chemically induced cell death.

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

“…As a result, redox cycling can ensue and produce large amounts of superoxide, which can dismutate to form H 2 O 2 or form more toxic ROS via intracellular metal-catalyzed reactions (O'Brien, 1991;Venugopal et al, 1996aVenugopal et al, , 1996bJamison et al, 2001Jamison et al, , 2002Jamison et al, , 2004. This redox cycling generates oxidative stress (Bellomo et al, 1982;Cohen and Slubberfield, 1990) and results in a number of deleterious effects on T24 cells, including depletion of NADPH (Akman et al, 1985) and reduced glutathione (Carbonera and Azzone, 1988;Bellomo et al, 1990;Cohen and Stubberfield, 1990;Fawthrop et al, 1991) with the oxidation of sulfhydryl groups in proteins, especially microtubules and other cytoskeletal proteins, such as the cytokeratins (Bellomo et al, 1990;Malorni et al, 1991;Wu et al, 1993aWu et al, , 1993bJarabak and Jarabak, 1995). Even minor quinone-induced peroxidation can damage cellular calcium transport systems and result in excess intracellular Ca 2ϩ levels that can also damage the cells.…”

“…If the cells are ischemic, oncotic swelling of most cellular compartments contributes to the irreversible destruction of the organelles and the cells (oncosis). The resulting (cell) corpses are then removed by macrophages and usually trigger an exudative inflammatory reaction (Majno et al, 1960;Wyllie et al, 1981;Fawthrop et al, 1991;Majno and Joris, 1995).…”

Regulation of P2X7 gene transcription

“…Apoptosis is a regulated homeostatic process of selective cell deletion [1][2][3], and it controls the growth of cells [4]. Dysregulation of apoptotic cell death has been implicated in states of disease and in the neoplastic transformation [5,6].…”

Protective effect of green tea polyphenols on tributyltin‐induced oxidative damage detected by in vivo and in vitro models

“…TBT-related toxicities, especially immunotoxicity, reproductive toxicity, and neurotoxicity, have been well documented (Fawthrop et al, 1991;Gennari et al, 2002).…”