Ribavirin-induced resistance to heat shock, inhibition of the Ras-Raf-1 pathway and arrest in G1

摘要: Abstract Ribavirin [1-(β- d -ribofuranosyl)1,2,4-triazole-3-carboxamide (virazole)], a specific inhibitor of inositide 5′-monophosphate dehydrogenase (IMPDH), induces strong depletion GTP pools in IGR39 cells. After 3-day treatment, the cell cycle was reversibly arrested G 0 /G 1 , suggesting involvement process. The reduction content modified appearance microtubule network, as examined using immunofluorescence. However, dynamics repolymerisation were not altered. When cells displayed surprising resistance to 3-h period heat shock at 45°C. Considering lack coimmunoprecipitation p21ras with Raf-1, level GTP-associated and decrease activation extracellular signal-regulated protein kinases (ERK), also known mitogen-activated (MAP) kinase, ribavirin-treated cells, we suggest possible relationship between expression heat-shock proteins change, GTP-depleted regulation Raf kinase by ras protein.