Supramaximal secretagogue stimulation enhances heat shock protein expression in the rat pancreas.
Heat shock or stress proteins (HSPs) are synthesized by various cell types in response to different metabolic insults (e.g., hyperthermia). Although the function of HSPs is not fully understood, they are believed to be an evolutionary conserved intracellular defense mechanism. In an attempt to characterize the autoprotective potential of pancreatic acinar cells, we investigated the regulation of HSPs of the 70-kD family and the small HSP ubiquitin in vitro and in vivo during supramaximal cerulein stimulation. Infusion of the secretagogue cerulein induces a mild edematous form of pancreatitis in vivo and is characterized by a marked disturbance of the intracellular transport and segregation of enzymes. Synthesis of HSP70 mRNA is upregulated in isolated pancreatic lobules by either cerulein (100 nM) or hyperthermia (42 degrees C for 60 min). In contrast, expression of ubiquitin mRNA was not altered by either secretagogue treatment or hyperthermia. This heat shock-like response of pancreatic acinar cells could be reproduced in vivo: Pancreatitis was induced in male Wistar rats by intravenous infusion of supramaximal doses of cerulein (10 micrograms/kg/h). Analysis of mRNA expression revealed a significant upregulation of HSP70 RNA during supramaximal secretagogue stimulation. mRNA levels encoding for ubiquitin remained unchanged. Western blot analysis demonstrated that the transcriptional upregulation of HSP70 in vivo was reflected on the protein level. This study demonstrates that the marked intracellular disturbance observed in secretagogue-induced pancreatitis is associated with enhanced expression and synthesis of a major stress protein. Given the autoprotective potential of HSPs, this upregulation may indicate a self-defense mechanism of pancreatic acinar cells in experimental pancreatitis.
Weber
C K
CK
Department of Medicine I, University of Ulm, Germany.
Gress
T
T
Müller-Pillasch
F
F
Lerch
M M
MM
Weidenbach
H
H
Adler
G
G
D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D002108:Ceruletide / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics*; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014452:Ubiquitins / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; D002108:Ceruletide