There are many death receptors that promote a cell to undergo necrosis. One key player in the result of necrotic cell death is Receptor Interacting Serine/Threonine Protein Kinase 1 (RIP1) and Receptor Interacting Serine/Threonine Protein Kinase 3 (RIP3) which when combined they make a necrosome. (Jog) Tumor Necrosis Factor Receptor Type 1 - associated Death Domain (TRADD) is required for the recruitment of RIP1 and RIP3 to TNFR1. RIP1 activates Tumor Necrosis Factor alpha necrosis and its phosphorylating activity activates leads to signaling cascades in other necrotic death receptors such as Fas or Tumor Necrosis Factor Receptor 1 (TNFR1). TNFR1 is activated by the binding of a ligand, such as an initiator caspase, which leads to a conformational change of the receptor. RIP1 activates Nuclear Factor - kappa light chain enhancer of activated B cells (NF-kB.) Caspase 8 can inhibit this pathway from occurring and leads to anti-necrosis or anti-apoptotic pathway. The NF-kB pathway can be activated by TNFR1 but it can also be activated by a variety of bacterial toxins, pathogens or drugs. Some mediators of the necrotic pathway include reactive oxygen species (ROS), calcium, phospholipases, proteases and ceramide. ROS is created normally in the cell through complex I and complex II of the electron transport chain. There are scavengers that get rid of the ROS and free radicals so it does not affect the body negatively. However bacterial toxins or injury can lead to a change in the ratio of scavengers to ROS and lead to necrosis. Due to similar reasons, there can be an overproduction of Ca2+ which results
There are many death receptors that promote a cell to undergo necrosis. One key player in the result of necrotic cell death is Receptor Interacting Serine/Threonine Protein Kinase 1 (RIP1) and Receptor Interacting Serine/Threonine Protein Kinase 3 (RIP3) which when combined they make a necrosome. (Jog) Tumor Necrosis Factor Receptor Type 1 - associated Death Domain (TRADD) is required for the recruitment of RIP1 and RIP3 to TNFR1. RIP1 activates Tumor Necrosis Factor alpha necrosis and its phosphorylating activity activates leads to signaling cascades in other necrotic death receptors such as Fas or Tumor Necrosis Factor Receptor 1 (TNFR1). TNFR1 is activated by the binding of a ligand, such as an initiator caspase, which leads to a conformational change of the receptor. RIP1 activates Nuclear Factor - kappa light chain enhancer of activated B cells (NF-kB.) Caspase 8 can inhibit this pathway from occurring and leads to anti-necrosis or anti-apoptotic pathway. The NF-kB pathway can be activated by TNFR1 but it can also be activated by a variety of bacterial toxins, pathogens or drugs. Some mediators of the necrotic pathway include reactive oxygen species (ROS), calcium, phospholipases, proteases and ceramide. ROS is created normally in the cell through complex I and complex II of the electron transport chain. There are scavengers that get rid of the ROS and free radicals so it does not affect the body negatively. However bacterial toxins or injury can lead to a change in the ratio of scavengers to ROS and lead to necrosis. Due to similar reasons, there can be an overproduction of Ca2+ which results