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

E. M. Ortiz, N. J. Dusetti, S. Vasseur, D. Malka, H. Bodeker, C. Dagorn, J. L. Iovanna

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122 Scopus citations

Abstract

Background and 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 NFκB 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.

Original languageEnglish
Pages (from-to)808-816
Number of pages9
JournalGastroenterology
Volume114
Issue number4 I
DOIs
StatePublished - Apr 1998
Externally publishedYes

Bibliographical note

Funding Information:
Supported in part by a grant from the Société Nationale Française de Gastro-Entérologie; a fellowship from the Fondation pour la Recherche Médicale (to N.J.D.); a fellowship from Eurorga-Jouveinal (to E.M.O.); a predoctoral fellowship from the Ministère de la Recherche et de la Technologie (to S.V.); a Beaufour fellowship (to D.M.); and grant BO 1416/ 1-1 of the Deutsche Forschungsgemeinschaft (DFG) (to H.B.).

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