Mitogen-activated protein kinases trichothecene activation

What are the mechanisms by which trichothecenes exert their transcriptional and post-transcriptional effects The 60S ribosomal subunit is a well-known molecular target of trichothecenes in leukocytes and other actively proliferating eukaryotic cells,3 whereas attempts to demonstrate alternative receptors have not been successful.37 38 Translational inhibitors that bind to ribosomes rapidly activate mitogen-activated protein kinases (MAPKs) and apoptosis via a mechanism termed the ribotoxic stress response. 39-40... 

Shifrin, V. I. and Anderson P. Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis. J. Biol. Chem. 274, 13985, 1999. 

Zhou, H. R., Islam Z., and Pestka J.J. Rapid, sequential activation of mitogen-activated protein kinases and transcription factors precedes proinflammatory cytokine mRNA expression in spleens of mice exposed to the trichothecene vomitoxin. Toxicol. Sci. 72,130,2003. 

Trichothecenes are potent inhibitors of protein synthesis due to binding to the 60S ribosomal unit and this is believed to be the main mechanism of toxicity. However, recent experimental data suggest that activation of the mitogen-activated protein kinases (MAPKs) through the ribosomal stress response could be another mechanism that operates via apoptotic and proinflammatory processes. 

Trichothecenes inhibit synthesis of protein, RNA and DNA as well as mitochondrial and electron transport chain function stimulate lipid peroxidation alter cell membrane function induce apoptosis modulate immune responses activate mitogen-activated protein kinases (MAPKs) and induce gene expression of numerous chemokines and cytokines and alter neurotransmitter levels. 

---

See also in sourсe #XX -- [ , ]

---