Sodium arsenite induces heat shock protein 70 expression and protects against secretagogue-induced trypsinogen and NF-kappaB activation.
Heat shock proteins (HSPs), induced by a variety of stresses, are known to protect against cellular injury. Recent studies have demonstrated that prior beta-adrenergic stimulation as well as thermal or culture stress induces HSP70 expression and protects against cerulein-induced pancreatitis. The goal of our current studies was to determine whether or not a non-thermal, chemical stressor like sodium arsenite also upregulates HSP70 expression in the pancreas and prevents secretagogue-induced trypsinogen and NF-kappaB activation. We examined the effects of sodium arsenite preadministration on the parameters of cerulein-induced pancreatitis in rats and then monitored the effects of preincubating pancreatic acini with sodium arsenite in vitro. Our results showed that sodium arsenite pretreatment induced HSP70 expression both in vitro and in vivo and significantly ameliorated the severity of cerulein-induced pancreatitis, as evidenced by the markedly reduced degree of hyperamylasemia, pancreatic edema, and acinar cell necrosis. Sodium arsenite pretreatment not only inhibited trypsinogen activation and the subcellular redistribution of cathepsin B, but also prevented NF-kappaB translocation to the nucleus by inhibiting the IkappaBalpha degradation both in vivo and in vitro. We also examined the effect of sodium arsenite pretreatment in a more severe model of pancreatitis induced by L-arginine and found a similarly protective effect. Based on our observations we conclude that, like thermal stress, chemical stressors such as sodium arsenite also induce HSP70 expression in the pancreas and protect against acute pancreatitis. Thus, non-thermal pharmacologically induced stress can help prevent or treat pancreatitis.
Bhagat
Lakshmi
L
Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Singh
Vijay P
VP
Dawra
Rajinder K
RK
Saluja
Ashok K
AK
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000494:pharmacology*; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000199:Actins; D018053:Arsenites; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D017670:Sodium Compounds; C017947:sodium arsenite; D002108:Ceruletide; D000255:Adenosine Triphosphate; D014362:Trypsinogen; D001120:Arginine; D014357:Trypsin