TRIB3 alters endoplasmic reticulum stress-induced -cell apoptosis via the NF-B pathway. Academic Article uri icon

abstract

  • OBJECTIVE: To examine the effect of TRIB3 on endoplasmic reticulum stress induced -cell apoptosis and to investigate the mechanism with a specific emphasis on the role of NF-B pathway. MATERIALS/METHODS: We investigated the effect of TRIB3 on ER stress-induced -cell apoptosis in INS-1 cells and primary rodent islets. The potential role of TRIB3 in ER stress inducer thapsigargin (Tg)-induced -cell apoptosis was assessed using overexpression and siRNA knockdown approaches. Inducible TRIB3 -cells, regulated by the tet-on system, were used for sub-renal capsule transplantation in streptozotocin (STZ)-diabetic mice, to study the effect of TRIB3 on ER stress-induced -cell apoptosis in vivo. Apoptosis was determined by TUNEL staining both in vivo and in vitro, while the molecular mechanisms of NF-B activation were investigated. RESULTS: TRIB3 was induced in ER-stressed INS-1 cells and rodent islets, and its overexpression was accompanied by increased -cell apoptosis. Specifically, TRIB3 overexpression enhanced Tg-induced INS-1 derived -cell apoptosis both in vitro and in sub-renal capsular transplantation animal model. Additionally, knockdown of Trib3 blocked Tg-induced apoptosis. Mechanistically, the induction of TRIB3 during ER stress resulted in the activation of NF-B and aggravated INS-1 derived -cell apoptosis, while inhibiting the NF-B pathway significantly abrogated this response and prevented -cell apoptosis, both in vitro and in sub-renal capsular transplantation animal model. CONCLUSION: TRIB3 mediated ER stress-induced -cell apoptosis via the NF-B pathway.

published proceedings

  • Metabolism

author list (cited authors)

  • Fang, N. i., Zhang, W., Xu, S., Lin, H., Wang, Z., Liu, H., ... Lou, J.

complete list of authors

  • Fang, Ni||Zhang, Wenjian||Xu, Shiqing||Lin, Hua||Wang, Zai||Liu, Honglin||Fang, Qing||Li, Chenghui||Peng, Liang||Lou, Jinning

publication date

  • June 2014