Characterization of TNF-induced caspase-independent necroptosis.
Caspase-independent programmed necrotic cell death (necroptosis) has recently been described. Previously described models of necroptosis required 16h or more of induction, which made the interpretation of findings somewhat difficult. In human monocytic leukemia cell line U937 necroptosis could be induced within 6h by combination of TNF and Z-VAD-fmk. Here we show that the reduction in intracellular ATP levels may not be the sole determinant of necroptosis, and that necroptosis is associated with the loss of mitochondrial membrane potential, but not the activation of Bak/Bax or calcineurin.
Department of Internal Medicine, Osaka Dental University, Osaka, Japan. Electronic address: sawai@cc.osaka-dent.ac.jp.
Hirofumi
H
Sawai
D000255:Adenosine Triphosphate / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D065095:Calcineurin Inhibitors; D020169:Caspases / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis; D011487:Protein Conformation; D052999:Quinazolinones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000737:chemistry
C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; C494772:BAK1 protein, human; C494826:BAX protein, human; D065095:Calcineurin Inhibitors; D007093:Imidazoles; D007211:Indoles; D052999:Quinazolinones; D014409:Tumor Necrosis Factor-alpha; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C507699:necrostatin-1; D000255:Adenosine Triphosphate; D020169:Caspases
ATP; Apoptosis; Caspase; Necroptosis; TNF