The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis

Gastroenterology. 1998 Apr;114(4):808-16. doi: 10.1016/s0016-5085(98)70595-5.


Background & aims: Free radicals are involved in the pathogenesis of acute pancreatitis, during which pancreatitis-associated protein (PAP)-I is overexpressed. We explored whether PAP-I expression could be induced by oxidative stress and whether it could affect apoptosis.

Methods: AR4-2J cells were exposed to H2O2 or menadione, and PAP-I messenger RNA (mRNA) expression was analyzed by Northern blotting.

Results: Maximal expression was observed with 0.1 mmol/L H2O2 or with 0.05 mmol/L menadione. Induction was detectable after 12 hours, reached a climax at 18 hours, and then decreased. Pretreatment of the cells with pyrrolidine dithiocarbamate completely abolished PAP-I mRNA induction, suggesting involvement of NFkappaB in the signaling pathway. These findings were confirmed in transient transfection assays using a plasmid containing the PAP-I promoter linked to the chloramphenicol acetyltransferase reporter gene. Then the relationship between PAP-I induction and protection against cell damage during oxidative stress was considered. Constitutive PAP-I expression in AR4-2J cells after transfection with PAP-I complementary DNA conferred significant resistance to apoptosis induced by low doses of H2O2 but not to necrosis induced by high doses of H2O2.

Conclusions: These results suggest that during oxidative stress, PAP-I might be part of a mechanism of pancreatic cell protection against apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis*
  • Acute-Phase Proteins / genetics
  • Antigens, Neoplasm*
  • Antioxidants / pharmacology
  • Apoptosis*
  • Biomarkers, Tumor*
  • Cell Line
  • Free Radicals
  • Hydrogen Peroxide / toxicity
  • Lectins, C-Type*
  • Oxidative Stress
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatitis-Associated Proteins
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis


  • Acute-Phase Proteins
  • Antigens, Neoplasm
  • Antioxidants
  • Biomarkers, Tumor
  • Free Radicals
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • REG3A protein, human
  • RNA, Messenger
  • Hydrogen Peroxide