title: Coupled induction of exocrine proteins and intracellular compartments involved in the secretory pathway in AR4-2J cells by glucocorticoids.
abstract: Treatment of AR4-2J cells with dexamethasone at 10 nM for 96 h inhibited cell replication by 75% and increased cell size (30%), protein content (1.6-fold) and protein synthesis (2-fold). The increase in protein synthesis was largely due to a 5 to 10-fold increase in the synthesis of secretory proteins. Amylase activity increased 20 to 30-fold in cellular homogenates and 10 to 20-fold in culture medium. Both in the presence and absence of dexamethasone AR4-2J cells release their secretory proteins by constitutive secretion. The proportion of newly synthesized amylase retained by the cells over the 14 h labeling period increased from 15 to 30% with hormone treatment. As judged by comigration on polyacrylamide gels and Western blots analyzed by immunospecific sera, AR4-2J cells synthesize and secrete the majority of known pancreatic secretory proteins. Dexamethasone increased the synthesis of trypsinogen 12 to 16-fold, chymotrypsinogen 4.5 to 6-fold, the group of procarboxypeptidases 6-fold, and amylase 7 to 10-fold. Messenger RNA levels for trypsinogen, amylase and lipase were each increased 4 to 5-fold. At the ultrastructural level dexamethasone led to significant increases in rough endoplasmic reticulum (RER) (30-fold) and Golgi elements (1.5-fold) and to the de novo appearance of electron-opaque granules (0.1-0.5 microns) which were shown to contain amylase by immunolocalization techniques employing protein A-gold. Dexamethasone also led to the formation of gap junctions between AR4-2J cells. These findings indicate that AR4-2J cells provide a model for differentiation of pancreatic acinar cells which should also be studied for the differentiation markers for the regulated secretory pathway.
authors: Laboratory for Cell Biology and Cell Pathology, University of Marburg/Federal Republic of Germany.
authors: B
authors: B
authors: Swarovsky
authors: W
authors: W
authors: Steinhilber
authors: G A
authors: GA
authors: Scheele
authors: H F
authors: HF
authors: Kern
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line; D002919:Chymotrypsinogen / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D005938:Glucocorticoids / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D014362:Trypsinogen / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D005938:Glucocorticoids; D009363:Neoplasm Proteins; D014362:Trypsinogen; D002919:Chymotrypsinogen; D000681:Amylases; D002268:Carboxypeptidases