ATM and P53 differentially regulate pancreatic beta cell survival in Ins1E cells

• DOI: 10.1371/journal.pone.0237669
• Publication Date: 2020-08-18T18:07:15Z
• Authors: Celina Uhlemeyer; Nadine Müller; Kerstin Grieß; Corinna Wessel; Caroline Schlegel; Jennifer Kuboth; Bengt-Frederik Be...
• Keywords: 0301 basic medicine; Cell Survival; Science; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Streptozocin; Cell Line; 03 medical and health sciences; Insulin-Secreting Cells; Diabetes Mellitus; Animals; Humans; Protease Inhibitors; RNA, Small Interfering; Tunicamycin; Q; R; Endoplasmic Reticulum Stress; Rats; Gene Knockdown Techniques; Medicine; Tumor Suppressor Protein p53; Protein Processing, Post-Translational; Research Article; DNA Damage; Signal Transduction

Pancreatic beta cell death is a hallmark of type 1 and 2 diabetes (T1D/T2D), but the underlying molecular mechanisms are incompletely understood. Key proteins DNA damage response (DDR), including tumor protein P53 (P53, also known as TP53 or TRP53 in rodents) Ataxia Telangiectasia Mutated (ATM), kinase to act upstream P53, have been associated with T2D. Here we test compare effect ATM ablation on survival rat line Ins1E. We demonstrate that differentially regulate apoptosis induced upon fundamentally different types diabetogenic stress, damage, inflammation, lipotoxicity endoplasmic reticulum (ER) stress. by treatment commonly used agent streptozotocin (STZ) regulated both P53. show key STZ activator amelioration inhibition mainly depends While control lipotoxic apoptosis, not fails alter inflammatory death. In contrast, tunicamycin (ER stress associated) further increased knockdown inhibition, knockdown. Our results reveal differential roles for vitro context four pathophysiological indicate can use independent signaling pathways modify survival, dependent cellular insult.