<unk> s accelerates reactive oxygen species production in cells, which in turn mediates the induction of the programmed cell death pathway in cells The toxicity of<unk> s is primarily the result of their widely cited action as protein synthesis inhibitors; this inhibition occurs at ribosomes during all three stages of protein synthesis: initiation, elongation, and termination. During initiation,<unk> s can either inhibit the association of the two ribosomal subunits, or inhibit the function of the mature ribosome by preventing the association of the first tRNA with the start codon. Inhibition at elongation most likely occurs due to<unk> s preventing the function peptidyl transferase, the enzyme which catalyzes the formation of new peptide bonds on the 60s ribosomal subunit. Inhibition during termination can also be the result of peptidyl transferase inhibition or the ability of<unk> s to prevent the hydrolysis required at this final step. It is interesting to note that the substitution pattern of the ring core of<unk> s influences the toxin's action as either an inhibitor of initiation or as an inhibitor of elongation/termination.<unk> s also have the ability to affect general cellular enzyme function due to the tendency of active site thiol groups to attack the 12,13 carbon epoxide ring. These inhibitory effects are seen most dramatically in actively proliferating cells such as in the gastrointestinal tract or the bone marrow. Protein synthesis occurs in both the cytoplasm of the cell as well as in the luminal space of mitochondria, the cytoplasmic organelle responsible for producing the cell's energy. This is done through an enzymatic pathway that generates highly oxidized molecules called reactive oxygen species, for example hydrogen peroxide. Reactive oxygen species can react with and cause damage to many critical parts of the cell including membranes, proteins, and DNA.<unk>  inhibition of protein synthesis in the mitochondria allows reactive oxygen species to build up in the cell which inevitably leads to oxidative stress and induction of the programmed cell death pathway, apoptosis. The induction of apoptosis in cells with high levels of reactive oxygen species is due to a variety of cell signaling pathways. The first is the p53 pathway which is shown to be upregulated by the T-2 toxin. p53 is a protein responsible for controlling the cell cycle, but an increase in the activity of this protein also leads to increased activation of BAX proteins in the cell. These BAX proteins are primarily responsible for increasing the permeability of the mitochondrial membrane and leading to the release of cytochrome c and reactive oxygen species. Release of cytochrome c from the mitochondria induces apoptosis by initiating the assembly of caspases, or proteins responsible for degrading the cell from within. Additionally,<unk> s such as T-2, have also been shown to increase the c-Jun N-Terminal Kinase signaling pathway in cells. Here, c-Jun N-Terminal Kinase is able to increase to phosphorylation of its target, c-Jun, into its active form. Activated c-jun acts as a transcription factor in the cell nucleus for proteins important for facilitating the downstream apoptotic pathway.
Trichothecene
Scyllatoxin
Laudanum
Toxicon
Simmondsin
Coal tar
Mersa
Chloracne