The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis
| Autor: | Jean Charles Dagorn, Juan L. Iovanna, Hans Bödeker, David Malka, Emilia M. Ortiz, Sophie Vasseur, Nelson Dusetti |
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| Rok vydání: | 1998 |
| Předmět: |
Free Radicals
Apoptosis Pancreatitis-Associated Proteins Biology medicine.disease_cause Antioxidants Cell Line chemistry.chemical_compound Menadione Pyrrolidine dithiocarbamate Antigens Neoplasm Biomarkers Tumor medicine Lectins C-Type RNA Messenger Promoter Regions Genetic Pancreas Cell damage Reporter gene Hepatology Gastroenterology Hydrogen Peroxide Transfection medicine.disease Molecular biology Oxidative Stress chemistry Biochemistry Signal transduction Oxidative stress Acute-Phase Proteins |
| Zdroj: | Gastroenterology. 114:808-816 |
| ISSN: | 0016-5085 |
| DOI: | 10.1016/s0016-5085(98)70595-5 |
| Popis: | 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 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. GASTROENTEROLOGY 1998;114:808-816 |
| Databáze: | OpenAIRE |
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