Biomaterial Database

TNFalpha and reactive oxygen species in necrotic cell death. 2008

Michael J Morgan, and You-Sun Kim, and Zheng-gang Liu

Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Death receptors, including the TNF receptor-1 (TNF-RI), have been shown to be able to initiate caspase-independent cell death. This form of "necrotic cell death" appears to be dependent on the generation of reactive oxygen species. Recent data have indicated that superoxide generation is dependent on the activation of NADPH oxidases, which form a complex with the adaptor molecules RIP1 and TRADD. The mechanism of superoxide generation further establishes RIP1 as the central molecule in ROS production and cell death initiated by TNFalpha and other death receptors. A role for the sustained JNK activation in necrotic cell death is also suggested. The sensitization of virus-infected cells to TNFalpha indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells.

UI	MeSH Term	Description	Entries
D009336	Necrosis	The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013481	Superoxides	Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.	Superoxide Radical,Superoxide,Superoxide Anion
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D014777	Virus Diseases	A general term for diseases caused by viruses.	Viral Diseases,Viral Infections,Virus Infections,Disease, Viral,Disease, Virus,Diseases, Viral,Diseases, Virus,Infection, Viral,Infection, Virus,Infections, Viral,Infections, Virus,Viral Disease,Viral Infection,Virus Disease,Virus Infection
D016601	RNA-Binding Proteins	Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.	Double-Stranded RNA-Binding Protein,Double-Stranded RNA-Binding Proteins,ds RNA-Binding Protein,RNA-Binding Protein,ds RNA-Binding Proteins,Double Stranded RNA Binding Protein,Double Stranded RNA Binding Proteins,Protein, Double-Stranded RNA-Binding,Protein, ds RNA-Binding,RNA Binding Protein,RNA Binding Proteins,RNA-Binding Protein, Double-Stranded,RNA-Binding Protein, ds,RNA-Binding Proteins, Double-Stranded,ds RNA Binding Protein
D047888	Receptors, Tumor Necrosis Factor, Type I	A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.	Antigens, CD120a,CD120a Antigens,Receptors, Tumor Necrosis Factor, Member 1A,Tumor Necrosis Factor Receptor Superfamily, Member 1A,Tumor Necrosis Factor Receptor Type I,CD 120a Antigen,CD120a Antigen,TNFR p60,TNFR-I,TNFR1,TNFRSF1A (Tumor Necrosis Factor Receptor Superfamily, Member 1A),TNFRSF1A Receptor,Tumor Necrosis Factor Receptor 1A,Tumor Necrosis Factor Receptor Type 1,120a Antigen, CD,Antigen, CD 120a,Antigen, CD120a,Receptor, TNFRSF1A
D048670	MAP Kinase Kinase 4	A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.	JN Kinase Kinase,JNK Kinase,JNK-Activating Protein Kinase,JNKK1 Protein Kinase,Jun Amino-Terminal Kinase Kinase,MEK4 Protein Kinase,Mitogen-Activated Protein Kinase Kinase 4,SAP Kinase Kinase 1,SAP Kinase-Extracellular Signal-Regulated Kinase Kinase 1,SAPK-ERK Kinase 1,SEK1 Protein Kinase,Stress-Activated Protein Kinase Kinase 1,JNK Activating Protein Kinase,Jun Amino Terminal Kinase Kinase,Kinase, JNKK1 Protein,Mitogen Activated Protein Kinase Kinase 4,Protein Kinase, JNK-Activating,Protein Kinase, JNKK1,Protein Kinase, MEK4,Protein Kinase, SEK1,SAP Kinase Extracellular Signal Regulated Kinase Kinase 1,SAPK ERK Kinase 1,Stress Activated Protein Kinase Kinase 1