biostudies-literatureRoest GNorges ForskningsrådFonds Wetenschappelijk OnderzoekE239https://www.ebi.ac.uk/biostudies/studies/S-EPMC6316609biostudies-literatureUnknown7(12)Accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) to reduce protein load and restore homeostasis, including via induction of autophagy. We used the proline analogue l-azetidine-2-carboxylic acid (AZC) to induce ER stress, and assessed its effect on autophagy and Ca²⁺ homeostasis. Treatment with 5 mM AZC did not induce poly adenosine diphosphate ribose polymerase (PARP) cleavage while levels of binding immunoglobulin protein (BiP) and phosphorylated eukaryotic translation initiation factor 2α (eIF2α) increased and those of activating transcription factor 6 (ATF6) decreased, indicating activation of the protein kinase RNA-like ER kinase (PERK) and the ATF6 arms of the UPR but not of apoptosis. AZC treatment in combinCellsThe ER Stress Inducer l-Azetidine-2-Carboxylic Acid Elevates the Levels of Phospho-eIF2α and of LC3-II in a Ca²⁺-Dependent Manner.PMC6316609230686G063413NG092715NBultynck GHesemans EWelkenhuyzen KEngedal NParys JBRoest GLuyten TfalseThe ER Stress Inducer l-Azetidine-2-Carboxylic Acid Elevates the Levels of Phospho-eIF2α and of LC3-II in a Ca²⁺-Dependent Manner.Accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) to reduce protein load and restore homeostasis, including via induction of autophagy. We used the proline analogue l-azetidine-2-carboxylic acid (AZC) to induce ER stress, and assessed its effect on autophagy and Ca²⁺ homeostasis. Treatment with 5 mM AZC did not induce poly adenosine diphosphate ribose polymerase (PARP) cleavage while levels of binding immunoglobulin protein (BiP) and phosphorylated eukaryotic translation initiation factor 2α (eIF2α) increased and those of activating transcription factor 6 (ATF6) decreased, indicating activation of the protein kinase RNA-like ER kinase (PERK) and the ATF6 arms of the UPR but not of apoptosis. AZC treatment in combin2018-01-01T00:00:00Z2018 Nov2025-04-22T07:31:00.199Z2019-03-26T22:36:51ZS-EPMC63166093051358810.3390/cells7120239