IP3R-Mediated Calcium Release Promotes Ferroptotic Death in SH-SY5Y Neuroblastoma Cells

• DOI: 10.20944/preprints202401.1838.v1
• Publication Date: 2024-01-29T02:26:03Z
• Authors: Joaquín Campos; Silvia Gleitze; Cecilia Hidalgo; Marco T. Núñez
• Keywords: SH-SY5Y

Ferroptosis is an iron-dependent cell death pathway that involves depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. experimentally caused by inhibition the cystine/glutamate antiporter xCT, which depletes cells GSH, or Glutathione peroxidase 4 (GPx4), a key regulator The events occur between GPx4 execution ferroptotic are currently matter active research. Previous work has shown calcium release from endoplasmic reticulum (ER) mediated ryanodine receptor (RyR) channels contributes to ferroptosis-induced in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, do not express RyR channels, test if inositol 1,4,5-trisphosphate (IP3R) channel plays role this process. We show RAS Selective Lethal Compound 3 (RSL3) generated increase reactive oxygen species (ROS), increased cytoplasmic mitochondrial levels, peroxidation death. RSL3-induced signals were inhibited Xestospongin B, inhibitor ER-resident IP3R channel, decreasing with carbachol IP3R1 knock-down. chelator BAPTA-AM signals, affected extracellular depletion. propose activates IP3R-mediated leading turn stimulate production ROS induce noxious positive feedback cycle.