Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effects on proliferation and secretion

Abstract

The objectives of the present study were to determine the effect of nicotine on MAPK signaling and on the proliferation of AR42J cells as well as to assess the relationship between MAPK activation and exocrine secretion in these cells. AR42J cells were incubated with nicotine and analyzed for the activation of MAPK by Western blot analysis using their respective antibodies and confirmed by immunohistochemistry. The effect of nicotine on cell proliferation was determined by the spectrophotometric method, and cell function was assessed by cholecystokinin (CCK)-stimulated amylase release into the culture medium. Nicotine at a dose of 100 microM induced phospho-ERK1/2 activation maximally in 3 min compared with untreated cells. Furthermore, immunofluorescence study confirmed the nicotine-induced increase in translocation of phospho-ERK1/2 to the nucleus. Activation of phospho-ERK1/2 was inhibited by an ERK1/2 pathway inhibitor but not by a nicotine receptor antagonist. At the same dose, there was significantly enhanced proliferation of AR42J cells until 72 h without toxic effect, as the percentage of lactate dehydrogenase release remained unchanged. Other MAPKs, c-Jun NH2-terminal kinase 1/2 and p38 MAPK, were not affected by nicotine treatment. At a nicotine dose of 100 microM, the CCK-stimulated release of amylase was maximal at 6 min, and, although a nicotinic receptor antagonist inhibited this response, it was not inhibited by the ERK1/2 pathway inhibitor. We conclude that nicotine treatment induced activation of ERK1/2 and increased the proliferation of AR42J cells. The data further indicate that MAPK signaling by nicotine is independent of the secretory response.

Nicotine Induces Hypoxia-Inducible Factor-1α Expression in Human Lung Cancer Cells via Nicotinic Acetylcholine Receptor–Mediated Signaling Pathways

“…Nicotine exerts its biological effects by binding to the nAChRs, thus leading to the activation of a cascade of signaling pathways (44), which include the influx of Ca 2+ and activation of calmodulin, PKC (40,45), c-Src, Janus-activated kinase 2/signal transducers and activators of transcription 3 (11, 38 -40), PI3K/Akt/mammalian target of rapamycin (5,35,46), and Raf-1/mitogen-activated protein kinase/ERK1/2 (7,34,45). In the present study, we also showed that nicotine activates both PI3K/Akt and ERK1/2 signaling pathways (Fig.…”

Enteral Exclusion Increases Map Kinase Activation and Cytokine Production in a Model of Gallstone Pancreatitis

“…In dispersed pancreatic acini, the same group showed that CCK-8 and TNF-␣ initiate NF B activation by different PLC pathways that converge at the level of the protein kinase Cs (PKC-␦ and -) to mediate NF B activation [42] . A study investigating the effect of nicotine on AR42J cells showed that it activates ERK but not p38 or JNK [43] . Lysophosphatidylcholine, a phospholipid by-product generated by phospholipase A2, activated stress kinases (ERK, JNK, and p38) and increased the specific DNA-binding activity of NF B and AP-1 [44] .…”

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

“…Nicotine, one of the main chemicals in tobacco, is known to be the primary psychoactive ingredient that has been responsible for reinforced behavior in smokers. Previous studies have shown that nicotine exposure has been associated with a variety of organ damages [3], including its effects of on pancreatic acinar cells [4][5][6][7]. An exploratory study on the development of an animal model of acute pancreatitis following exposure to nicotine has been reported [8].…”