title: Hormonal regulation of protein disulfide isomerase and chaperone synthesis in the rat exocrine pancreas.
abstract: Folding and assembly of polypeptides translocated into the rough endoplasmic reticulum (RER) is facilitated by a set of resident proteins in the lumen of the RER. We studied the regulation of synthesis of the RER luminal proteins immunoglobulin heavy chain binding protein (BiP) and protein disulfide isomerase (PDI), and of the cytosolic stress 70 protein (hsc70) after hormonal stimulation of the pancreatic exocrine secretory pathway. Their rate of synthesis was assessed at both mRNA and protein levels and under two experimental conditions that are associated with large increases in exocrine production. After in vivo stimulation of the pancreas by either endogenous release of cholecystokinin (CCK) following proteinase inhibitor feeding (FOY-305) or by in vivo infusion of the pancreatic secretagogue cerulein, the relative rates of synthesis detected for BiP and PDI were enhanced 2.5 to 4-fold compared to control. Interestingly, the kinetics and the degree of hsc70 mRNA induction were almost identical to those of BiP and PDI, suggesting coordinated hormonal regulation of BiP, PDI as hormonal stimulation was even twice that following heat shock treatment. The mRNA levels of calreticulin (CaBP3) increased up to 2.3-fold with a kinetic comparable to that of BiP, PDI and hsc 70, while CaBP1 and the RER membrane proteins, ribophorin I and the signal recognition particle receptor did not show any changes in their relative mRNA amounts after hormonal stimulation. The increase in the rates of PDI and chaperone biosynthesis exceeds the associated increase in total protein biosynthesis. In vitro experiments, using transformed rat acinar cells (AR4-2J) in which pancreatic enzyme synthesis can be induced by glycocorticoid hormones, demonstrated that induction of PDI and chaperone mRNA synthesis preceded extensive mRNA expression of secretory proteins.
authors.affiliation: Department of Cell Biology and Cell Pathology, University of Marburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hensel
authors.forename: V
authors.initials: V
authors.lastname: Assmann
authors.forename: H F
authors.initials: HF
authors.lastname: Kern
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D037282:Calreticulin; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry; D002461:Cell Line, Transformed / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology*; D018833:Chaperonins; D003907:Dexamethasone / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D005786:Gene Expression Regulation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000737:chemistry; D006358:Hot Temperature; D007535:Isomerases / Q000096:biosynthesis* / Q000737:chemistry; D008297:Male; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012261:Ribonucleoproteins / Q000096:biosynthesis
chemical_list: D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D004952:Esters; D006146:Guanidines; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C034532:camostat; D016670:Gabexate; D003907:Dexamethasone; D002108:Ceruletide; D018833:Chaperonins; D007535:Isomerases; D019704:Protein Disulfide-Isomerases