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. Recently, an attempt to determine PSP/reg and PAP levels in sera of rats with acute pancreatitis showed a significant increase in PAP but failed to demonstrate changes in PSP/reg. Others reported that surgical manipulation of the pancreas, including sham controls, affected mRNA levels of PSP/reg. Neither report determined protein levels of PSP/reg.


METHODS
Rats were treated intraperitoneally with a supramaximal dose of caerulein to induce pancreatitis, a physiological dose of caerulein, or a saline injection. Pancreata were analyzed for PAP and PSP/reg using ELISAs. RNA was extracted for Northern blot analysis of PAP I, II, and III and PSP/reg mRNA.


RESULTS
Experimental induction of acute pancreatitis caused a coordinate increase in both PSP/reg and PAP. PAP showed an acute response and returned to low levels within 48 h while PSP/reg exhibited a more sustained response. Intraperitoneal application of a physiological dose of caerulein and even a saline injection caused an increase in PSP/reg.


CONCLUSIONS
PSP/reg and PAP levels are increased through similar mechanisms by physiological and supramaximal doses of caerulein. However, PSP/reg regulation appears to sustain high levels while PAP levels are more transient. Since the regulation of this protein family is affected even under mild stress, we define them as secretory stress proteins.
Graf
R
R
Pancreatitis Research Laboratory, Department of Visceral and Transplant Surgery, University Hospital, 8091 Zürich, Switzerland. rgf@chi.usz.ch
Schiesser
M
M
Lüssi
A
A
Went
Ph
P
Scheele
G A
GA
Bimmler
D
D
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002108:Ceruletide; D037181:Lectins, C-Type; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D010179:Pancreas / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D037181:Lectins, C-Type; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; D020033:Protein Isoforms; C000612141:REG3A protein, human; D012333:RNA, Messenger; C497616:Reg1a protein, rat; C000612144:Reg3b protein, rat; D002108:Ceruletide