2026-03-05T21:19:05Z https://ir.soken.ac.jp/oai

oai:ir.soken.ac.jp:00003287 2023-06-20T14:04:57Z 1:273

PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice 飯田, 香穂里 IIDA, Kaori LI, Yulin MCGRATH, Barbara C FRANK, Ami CAVENER, Douglas R © 2007 Iida et al; licensee BioMed Central Ltd. application/pdf Background Deficiency of the PERK eIF2α kinase in humans and mice results in postnatal exocrine pancreatic atrophy as well as severe growth and metabolic anomalies in other organs and tissues. To determine if the exocrine pancreatic atrophy is due to a cell-autonomous defect, the Perk gene was specifically ablated in acinar cells of the exocrine pancreas in mice. Results We show that expression of PERK in the acinar cells is required to maintain their viability but is not required for normal protein synthesis and secretion. Exocrine pancreatic atrophy in PERK-deficient mice was previously attributed to uncontrolled ER-stress followed by apoptotic cell death based on studies in cultured fibroblasts. However, we have found no evidence for perturbations in the endoplasmic reticulum or ER-stress and show that acinar cells succumb to a non-apoptotic form of cell death, oncosis, which is associated with a pronounced inflammatory response and induction of the pancreatitis stress response genes. We also show that mice carrying a knockout mutation of PERK's downstream target, ATF4, exhibit pancreatic deficiency caused by developmental defects and that mice ablated for ATF4's transcriptional target CHOP have a normal exocrine pancreas. Conclusion We conclude that PERK modulates secretory capacity of the exocrine pancreas by regulating cell viability of acinar cells. BioMed Central 2007-08-29 eng journal article VoR https://ir.soken.ac.jp/records/3287 17727724 https://doi.org/10.1186/1471-2121-8-38 10.1186/1471-2121-8-38 http://www.biomedcentral.com/about/license Copyright 14712121 BMC Cell Biology BMC Cell Biology 8 https://ir.soken.ac.jp/record/3287/files/1471-2121-8-38.pdf application/pdf 731.2 kB 2014-03-11