Cytotoxic mechanism of tumor necrosis factor-alpha.
Many intracellular pathways are set in motion by the binding of tumor necrosis factor (TNF) to its cell surface receptor. Major steps in the TNF-mediated cytotoxicity cascade include G protein-coupled activation of phospholipases, generation of free radicals, and damage to nuclear DNA by endonucleases. Ultimately the cells undergo apoptosis and die. Understanding how TNF initiates these pathways will facilitate the rational design of pharmaceuticals that can attenuate or potentiate the action of this important cytokine.
Larrick
J W
JW
Genelabs Incorporated, Redwood City, California 94063.
Wright
S C
SC
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D005609:Free Radicals; D005786:Gene Expression Regulation; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D015290:Second Messenger Systems / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D005609:Free Radicals; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha