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

doi:10.1016/S0016-5085(98)70595-5

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

Institut national de la santé et de la recherche médicale

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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 language	English
Pages (from-to)	808-816
Number of pages	9
Journal	Gastroenterology
Volume	114
Issue number	4 I
DOIs	https://doi.org/10.1016/S0016-5085(98)70595-5
State	Published - Apr 1998
Externally published	Yes

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.).

Funding

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.).

Funders	Funder number
Eurorga-Jouveinal
Ministère de la Recherche et de la Technologie	BO 1416/ 1-1
Deutsche Forschungsgemeinschaft
Société Nationale Française de Gastro-Entérologie
Fondation pour la Recherche Médicale

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10.1016/S0016-5085(98)70595-5

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@article{604c2adaff3348e1bb9a157d9860493f,

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

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.",

author = "Ortiz, {E. M.} and Dusetti, {N. J.} and S. Vasseur and D. Malka and H. Bodeker and C. Dagorn and Iovanna, {J. L.}",

note = "Funding Information: Supported in part by a grant from the Soci{\'e}t{\'e} Nationale Fran{\c c}aise de Gastro-Ent{\'e}rologie; a fellowship from the Fondation pour la Recherche M{\'e}dicale (to N.J.D.); a fellowship from Eurorga-Jouveinal (to E.M.O.); a predoctoral fellowship from the Minist{\`e}re 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.). ",

year = "1998",

month = apr,

doi = "10.1016/S0016-5085(98)70595-5",

language = "אנגלית",

volume = "114",

pages = "808--816",

journal = "Gastroenterology",

issn = "0016-5085",

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T1 - The pancreatitis-associated protein is induced by free radicals in AR4- 2J cells and confers cell resistance to apoptosis

AU - Ortiz, E. M.

AU - Dusetti, N. J.

AU - Vasseur, S.

AU - Malka, D.

AU - Bodeker, H.

AU - Dagorn, C.

AU - Iovanna, J. L.

N1 - 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.).

PY - 1998/4

Y1 - 1998/4

N2 - 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.

AB - 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.

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JF - Gastroenterology

IS - 4 I

ER -

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

Abstract

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Funding

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