Advanced search
1 file | 1.94 MB Add to list

Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells

Author
Organization
Project
Abstract
Endoplasmic reticulum (ER) stress-induced cellular dysfunction and death is associated with several human diseases. It has been widely reported that ER stress kills through activation of the intrinsic mitochondrial apoptotic pathway. Here we demonstrate that ER stress can also induce necroptosis, an receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL)-dependent form of necrosis. Remarkably, we observed that necroptosis induced by various ER stressors in L929 cells is dependent on tumor necrosis factor receptor 1 (TNFR1), but occurs independently of autocrine TNF or lymphotoxin α production. Moreover, we found that repression of either TNFR1, RIPK1 or MLKL did not protect the cells from death but instead allowed a switch to ER stress-induced apoptosis. Interestingly, while caspase inhibition was sufficient to protect TNFR1- or MLKL-deficient cells from death, rescue of the RIPK1-deficient cells additionally required RIPK3 depletion, indicating a switch back to RIPK3-dependent necroptosis in caspase-inhibited conditions. The finding that ER stress also induces necroptosis may open new therapeutic opportunities for the treatment of pathologies resulting from unresolved ER stress.
Keywords
ACTIVATION, DEATH, TNF-ALPHA, DOMAIN-LIKE, MOLECULAR-MECHANISMS, ER STRESS, MIXED LINEAGE KINASE, TUMOR-NECROSIS-FACTOR, KINASE-DEPENDENT APOPTOSIS, UNFOLDED-PROTEIN-RESPONSE

Downloads

  • 2405 15Saveljeva.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 1.94 MB

Citation

Please use this url to cite or link to this publication:

MLA
Saveljeva, S, SL Mc Laughlin, Peter Vandenabeele, et al. “Endoplasmic Reticulum Stress Induces Ligand-independent TNFR1-mediated Necroptosis in L929 Cells.” CELL DEATH & DISEASE 6 (2015): n. pag. Print.
APA
Saveljeva, S., Mc Laughlin, S., Vandenabeele, P., Samali, A., & Bertrand, M. (2015). Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells. CELL DEATH & DISEASE, 6.
Chicago author-date
Saveljeva, S, SL Mc Laughlin, Peter Vandenabeele, A Samali, and Mathieu Bertrand. 2015. “Endoplasmic Reticulum Stress Induces Ligand-independent TNFR1-mediated Necroptosis in L929 Cells.” Cell Death & Disease 6.
Chicago author-date (all authors)
Saveljeva, S, SL Mc Laughlin, Peter Vandenabeele, A Samali, and Mathieu Bertrand. 2015. “Endoplasmic Reticulum Stress Induces Ligand-independent TNFR1-mediated Necroptosis in L929 Cells.” Cell Death & Disease 6.
Vancouver
1.
Saveljeva S, Mc Laughlin S, Vandenabeele P, Samali A, Bertrand M. Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells. CELL DEATH & DISEASE. 2015;6.
IEEE
[1]
S. Saveljeva, S. Mc Laughlin, P. Vandenabeele, A. Samali, and M. Bertrand, “Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells,” CELL DEATH & DISEASE, vol. 6, 2015.
@article{5819112,
  abstract     = {Endoplasmic reticulum (ER) stress-induced cellular dysfunction and death is associated with several human diseases. It has been widely reported that ER stress kills through activation of the intrinsic mitochondrial apoptotic pathway. Here we demonstrate that ER stress can also induce necroptosis, an receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL)-dependent form of necrosis. Remarkably, we observed that necroptosis induced by various ER stressors in L929 cells is dependent on tumor necrosis factor receptor 1 (TNFR1), but occurs independently of autocrine TNF or lymphotoxin α production. Moreover, we found that repression of either TNFR1, RIPK1 or MLKL did not protect the cells from death but instead allowed a switch to ER stress-induced apoptosis. Interestingly, while caspase inhibition was sufficient to protect TNFR1- or MLKL-deficient cells from death, rescue of the RIPK1-deficient cells additionally required RIPK3 depletion, indicating a switch back to RIPK3-dependent necroptosis in caspase-inhibited conditions. The finding that ER stress also induces necroptosis may open new therapeutic opportunities for the treatment of pathologies resulting from unresolved ER stress.},
  articleno    = {e1587},
  author       = {Saveljeva, S and Mc Laughlin, SL and Vandenabeele, Peter and Samali, A and Bertrand, Mathieu},
  issn         = {2041-4889},
  journal      = {CELL DEATH & DISEASE},
  keywords     = {ACTIVATION,DEATH,TNF-ALPHA,DOMAIN-LIKE,MOLECULAR-MECHANISMS,ER STRESS,MIXED LINEAGE KINASE,TUMOR-NECROSIS-FACTOR,KINASE-DEPENDENT APOPTOSIS,UNFOLDED-PROTEIN-RESPONSE},
  language     = {eng},
  pages        = {10},
  title        = {Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells},
  url          = {http://dx.doi.org/10.1038/cddis.2014.548},
  volume       = {6},
  year         = {2015},
}

Altmetric
View in Altmetric
Web of Science
Times cited: