Receptor Interacting Protein 3 is Required for Arsenite-mediated Necroptosis

  • Young Sik Cho College of Pharmacy, Keimyung University, 1000 Sindang-dong, Dalseo-gu, Daegu 704-701, South Korea
Keywords: Arsenite, Heat shock protein 90, programmed necrosis, receptor interacting protein 3


Arsenic compounds such as sodium arsenite (SA) and arsenic trioxide (ATO) are toxic to human. Primarily, we pursued to outline the cell death modes caused by arsenic compounds and to address what proteins would be responsible for arsenite-induced cytotoxicity. Both SA and ATO substantially exhibited cytotoxic activity in L929 cells. Necrostatin-1 (Nec-1) treatment significantly protected cell death mediated by arsenic compounds, suggesting that cells are committed to die in a programmed necrotic way. A geldanamycin analog DMAG destabilized receptor interacting protein 3 (RIP3) and concomitantly protected cells from SA toxicity. Using interfering RNAs, we eventually found that RIP3 was responsible for its antagonizing effects on SA. Therefore, it is proposed that arsenic compounds execute necroptotic cell death of L929 via a RIP3 dependent pathway.


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