Coordinate regulation of PSP/reg and PAP isoforms as a family of secretory stress proteins in an animal model of chronic pancreatitis.

Background: PSP/reg and PAP are secretory stress proteins (SSP) and may be part of a protective mechanism. They share structural homologies and form insoluble fibrils after tryptic activation. To further explore the regulation of these proteins, we investigated the male WBN/Kob rat, a model of pancreatic inflammatory and fibrotic disease similar to chronic pancreatitis.

Coordinate regulation of secretory stress proteins (PSP/reg, PAP I, PAP II, and PAP III) in the rat exocrine pancreas during experimental acute pancreatitis.

Background: Pancreatic stone protein (PSP/reg) is a constitutively secreted protein in pancreatic juice. Pancreatitis-associated protein (PAP) belongs to the same family of proteins. PAP is highly increased during acute pancreatitis, while no exact data exist regarding PSP/reg protein synthesis and secretion.

Pancreatic acinar cell dysfunction in CFTR(-/-) mice is associated with impairments in luminal pH and endocytosis.

Background & Aims: We have previously shown that endocytosis at the apical plasma membrane in pancreatic acinar cells is coupled to ductal bicarbonate secretion into the lumen. We hypothesized that decreased bicarbonate secretion in cystic fibrosis (CF) inhibits apical endocytosis. The aim of this study was to determine in cftr(-/-) mice (1) if the pH of the pancreatic juice is acidic compared with wild-type (WT) controls, (2) if there is a selective block in endocytosis, and (3) if alkalinization of the luminal fluid reverses this defect.

A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation.

A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases.

Regulation of PSP/reg in rat pancreas: immediate and steady-state adaptation to different diets.

Pancreatic stone protein/reg protein (PSP/reg) is a secretory pancreatic protein of hitherto unknown function. It is precursor to a spontaneously precipitating peptide called pancreatic thread protein, which is found in protein plugs within the pancreatic ductal system. Increasing PSP/reg concentrations in pancreatic juice might augment the risk of intraductal plug formation and therefore be a condition predisposing to chronic pancreatitis.