Sodium arsenite induces heat shock protein 70 expression and protects against secretagogue-induced trypsinogen and NF-κB activation

Lakshmi Bhagat, Vijay P. Singh, Rajinder Dawra, Ashok Saluja

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Heat shock proteins (HSPs), induced by a variety of stresses, are known to protect against cellular injury. Recent studies have demonstrated that prior β-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-κB 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-κB translocation to the nucleus by inhibiting the IκBα 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.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalJournal of Cellular Physiology
Volume215
Issue number1
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Trypsinogen
HSP70 Heat-Shock Proteins
Pancreatitis
Chemical activation
Ceruletide
Pancreas
Hot Temperature
Hyperamylasemia
Cathepsin B
Acinar Cells
Heat-Shock Proteins
sodium arsenite
Thermal stress
Adrenergic Agents
Arginine
Rats
Edema
Necrosis
Up-Regulation
Degradation

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Sodium arsenite induces heat shock protein 70 expression and protects against secretagogue-induced trypsinogen and NF-κB activation. / Bhagat, Lakshmi; Singh, Vijay P.; Dawra, Rajinder; Saluja, Ashok.

In: Journal of Cellular Physiology, Vol. 215, No. 1, 01.04.2008, p. 37-46.

Research output: Contribution to journalArticle

@article{21dd20d36cc4464682ea0b70d3d5bfe3,
title = "Sodium arsenite induces heat shock protein 70 expression and protects against secretagogue-induced trypsinogen and NF-κB activation",
abstract = "Heat shock proteins (HSPs), induced by a variety of stresses, are known to protect against cellular injury. Recent studies have demonstrated that prior β-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-κB 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-κB translocation to the nucleus by inhibiting the IκBα 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.",
author = "Lakshmi Bhagat and Singh, {Vijay P.} and Rajinder Dawra and Ashok Saluja",
year = "2008",
month = "4",
day = "1",
doi = "10.1002/jcp.21286",
language = "English (US)",
volume = "215",
pages = "37--46",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Sodium arsenite induces heat shock protein 70 expression and protects against secretagogue-induced trypsinogen and NF-κB activation

AU - Bhagat, Lakshmi

AU - Singh, Vijay P.

AU - Dawra, Rajinder

AU - Saluja, Ashok

PY - 2008/4/1

Y1 - 2008/4/1

N2 - Heat shock proteins (HSPs), induced by a variety of stresses, are known to protect against cellular injury. Recent studies have demonstrated that prior β-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-κB 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-κB translocation to the nucleus by inhibiting the IκBα 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.

AB - Heat shock proteins (HSPs), induced by a variety of stresses, are known to protect against cellular injury. Recent studies have demonstrated that prior β-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-κB 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-κB translocation to the nucleus by inhibiting the IκBα 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.

UR - http://www.scopus.com/inward/record.url?scp=39149109341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39149109341&partnerID=8YFLogxK

U2 - 10.1002/jcp.21286

DO - 10.1002/jcp.21286

M3 - Article

C2 - 17941083

AN - SCOPUS:39149109341

VL - 215

SP - 37

EP - 46

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 1

ER -