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Pathways to Cell Death in Hyperoxia*

Stuart Horowitz, PhD
Author and Funding Information

*From the Jewish Hospital Heart and Lung Institute, Louisville, KY Supported in part by a grant from the National Institutes of Health (HL02791), American Lung Association, Basic Grant FY-97-0590 from the March of Dimes Birth Defects Foundation, and Winthrop-University Hospital.

Correspondence to: Stuart Horowitz, PhD, Director, Research and Technology, Jewish Hospital Heart and Lung Institute, 217 E Chestnut St, Louisville, KY 40202; e-mail: stuart.horowitz@jhhs.org



Chest. 1999;116(suppl_1):64S-67S. doi:10.1378/chest.116.suppl_1.64S
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A widely held opinion about cell death is that apoptosis follows a series of events that are genetically programmed and necrosis does not. This simple-minded notion is partially due to the problem that most thinking about cell death is dichotomous: cell death is either apoptosis or necrosis. Thus, necrosis is currently the term used to describe slow death associated with swelling from hyperoxia or low concentrations of oxidants,1 as well as very rapid death at extremely high oxidant doses,2 in addition to almost every other form of nonapoptotic, unscheduled death due to any number of catastrophic insults. Necrosis may be too vague a term to be of much use in this regard, and it is probably best to think of necrosis as a consequence, rather than a mode of cell death, because even apoptosis can eventually result in “secondary necrosis.”3 However, it is conceivable that there are other modes of programmed cell death in addition to apoptosis, all of which currently fall under the heading of necrosis. So far, we are limited by the fact that the overwhelming majority of the tools available for the study of cell death have arisen from investigations of apoptosis. Recent progress in our laboratory indicates that hyperoxia-induced, nonapoptotic cell death is pathway driven, and that the pathways are at least partially divergent from those leading to apoptosis in the same cells. Herein we summarize these observations and discuss their implications.

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