Langenbeck's Archives of Surgery

, Volume 393, Issue 4, pp 547–555

A cell-based approach to study changes in the pancreas following nicotine exposure in an animal model of injury

Original Article

Abstract

Background

Cigarette smoking is a recognized risk factor for the induction of pancreatic diseases and is suspected to play a major role in the development of pancreatic cancer in smokers.

Materials and methods

This study was designed to characterize the mechanisms of nicotine-induced injury to the pancreas. AR42Jcells, a stable mutant pancreatic tumor cell line, was chosen for the study because of its stability in culture media and also because of its known secretory capacity, which is like that of a normal pancreatic acinar cell. It is hypothesized that nicotine-induced effects on the pancreas are triggered by oxidative stress induced in pancreatic acinar cell via oxidative stress signaling pathways.

Results

The results from our study showed that, in vitro, nicotine induced generation of oxygen free radicals measured as malondialdehyde, an end product of lipid peroxidation. Treatment of AR42J cells with nicotine induced p-ERK 1/2 activation as confirmed by Western blot and immunofluorescence imaging of cytoplasmic localization of mitogen-activated protein kinase (MAPK) signals. Nicotine enhanced AR42J cell proliferation and cholecystokinin-stimulated amylase release in AR42J cells. These effects of nicotine were confirmed by simultaneous studies conducted on the same cells by hydrogen peroxide, a known oxidative biomarker. Allopurinol, a XOD inhibitor, suppressed these effects induced by nicotine and H2O2 with the exception that cholecystokinin-stimulated amylase release by H2O2 remained unaltered when AR42J cells were preincubated with allopurinol. These results suggest that nicotine-induced effects on pancreatic acinar cells were associated with generation of oxyradical mediated via the XOD pathway. The results have a direct impact on cell proliferation, MAPK signaling, and acinar cell function.

Conclusion

We conclude that nicotine induces oxidative stress in pancreatic acinar cells and that these events trigger pathophysiological changes in the pancreas, leading to increased cell proliferation and injury.

Keywords

Nicotine AR42J cell Effect on mechanisms Lipid peroxidation MAPK signaling Cell function 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Physiology & Biophysics, Slot # 505University of Arkansas for Medical SciencesLittle RockUSA

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