| First Author | Kim HS | Year | 2005 |
| Journal | Biochem Biophys Res Commun | Volume | 336 |
| Issue | 3 | Pages | 847-53 |
| PubMed ID | 16154537 | Mgi Jnum | J:100857 |
| Mgi Id | MGI:3589832 | Doi | 10.1016/j.bbrc.2005.08.183 |
| Citation | Kim HS, et al. (2005) IFN-gamma sensitizes MIN6N8 insulinoma cells to TNF-alpha-induced apoptosis by inhibiting NF-kappaB-mediated XIAP upregulation. Biochem Biophys Res Commun 336(3):847-53 |
| abstractText | Although X-linked inhibitor of apoptosis protein (XIAP) is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic beta-cell apoptosis remains unclear. Here, we found that: (i) XIAP level was inversely correlated with tumor necrosis factor (TNF)-alpha-induced apoptosis in MIN6N8 insulinoma cells; (ii) adenoviral XIAP overexpression abrogated the TNF-alpha-induced apoptosis through inhibition of caspase activity; (iii) downregulation of XIAP by antisense oligonucleotide or Smac peptide sensitized MIN6N8 cells to TNF-alpha-induced apoptosis; (iv) XIAP expression was induced by TNF-alpha through a nuclear factor-kappaB (NF-kappaB)-dependent pathway, and interferon (IFN)-gamma prevented such an induction in a manner independent of NF-kappaB, which presents a potential mechanism underlying cytotoxic IFN-gamma/TNF-alpha synergism. Taken together, our results suggest that XIAP is an important modulator of TNF-alpha-induced apoptosis of MIN6N8 cells, and XIAP regulation in pancreatic beta-cells might play an important role in pancreatic beta-cell apoptosis and in the pathogenesis of type 1 diabetes. |
