Free radicals and apoptosis: relationships with glutathione, thioredoxin, and the BCL family of proteins.
Cellular fate is controlled by a number of factors within the cell, including an abundance of, and defenses against, free radicals generated both endogenously and exogenously. Free radical species are involved in regulating various growth, differentiation and death processes including apoptosis. Apoptosis is a preferred form of cell death because it is highly ordered resulting in the death of a cell with minimal effects on surrounding cells or tissues. Radicals generated during apoptosis directly modulate signaling cascades by activating or inhibiting survival transcription factors (i.e. NF-kappa B and AP-1), or more indirectly affecting such signaling by changing the cellular redox status [i.e. glutathione (GSH) and thioredoxin (Trx)]. At high levels, free radicals, including reactive oxygen species and various unwanted and harmful byproducts of reactions with tissue macromolecules, particularly lipids, can cause acute injury if not hindered by cellular antioxidants. These antioxidant protective systems are not only involved in preventing stress, but also maintaining the normal functioning of specific transcription factors and the bcl proteins. This review will discuss the association of reactive oxygen species with GSH, Trx and bcl proteins in apoptosis.
Kern
Julie C
JC
Division of Pharmaceutical Sciences, School of Pharmacy, The University of Wisconsin at Madison, Madison, WI 53706, USA. jckern@pharmacy.wisc.edu <jckern@pharmacy.wisc.edu>
Kehrer
James P
JP
D017209:Apoptosis / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D013879:Thioredoxins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D005227:Fatty Acids; D005609:Free Radicals; D014157:Transcription Factors; D019938:Cyclin D1; D013879:Thioredoxins; D005978:Glutathione