Reactive Oxygen Species Activate Mitogen-Activated Protein Kinases in Pancreatic Acinar Cells

Abstract

It has been recently reported that kinases that belong to the mitogen-activated protein kinase (MAPK) family are rapidly activated by cholecystokinin (CCK) in rat pancreas both in vitro and in vivo. It is known that reactive oxygen species (ROS) play an important role in the pathogenesis of acute pancreatitis induced by supraphysiologic stimulation with CCK analogue, cerulein. The aim of our study was to evaluate whether MAPKs are activated by ROS in pancreatic acini. The activity of MAPK, c-Jun amino-terminal kinase (JNK), and p38 MAPK was determined in isolated rat pancreatic acinar cells by means of Western blotting, with the use of specific antibody that recognizes active, dually phosphorylated kinases. Incubation of acini with ROS donors, hydrogen peroxide (H2O2) and/or menadione (MND), strongly activated all three kinases. Activation of these kinases by ROS, but not by CCK, was substantially inhibited by pretreatment of acini with antioxidant N-acetylo-L-cysteine (NAC). Whereas CCK-induced activation of MAPK or JNK was totally or partially blocked by protein kinase C (PKC) inhibitor GF-109203X, ROS-induced activation of MAPK, JNK, and p38 MAPK was PKC independent. In conclusion, ROS strongly activate MAPK, JNK, and p38 MAPK in pancreatic acinar cells. It may be of importance in acute pancreatitis, because ROS are involved in the pathogenesis of this disease.

Coagulation Abnormalities in Acute Pancreatitis

“…MAPKs are mammalian serine/threonine protein kinases known to amplify signals involved in differentiation, inflammation, and apoptosis (Robinson & Cobb, 1997). P38 MAPK and JNK/SAPK (c-Jun N-terminal kinase/stressactivated protein kinase) are stress-responding MAPKs which induce inflammatory pathways in the early pathogenesis of severe AP (Dabrowski et al, 2000;Samuel et al, 2003). In this study, severe AP was induced through retrograde infusion of a 5% sodium taurocholate solution via the pancreatic duct at 100 uL/min.…”

Hydrogen Peroxide-Induced Extracellular Signal-Regulated Kinase Activation in Cultured Feline Ileal Smooth Muscle Cells

“…It has been recently reported that p38 MAP kinase was activated in pancreatic acini by H 2 O 2 and menadione (Dabrowski et al, 2000). Therefore, the effect of H 2 O 2 on p38 MAP kinase was also examined in cultured ISMC.…”

“…To confirm that PKC is not involved in H 2 O 2 -induced ERK activation in ISMC, the effects of 3-[1-(dimethylaminopropyl)indol-3-yl]-4-(indol-3-yl)maleimide hydrochloride (GF109203X) (Dabrowski et al, 1997(Dabrowski et al, , 2000, a relatively specific PKC inhibitor, were also examined. Pretreatment of ISMC with 20 M GF109203X for 40 min had no effect on ERK activation by H 2 O 2 (Fig.…”

“…Also, three major MAP kinase signaling cascades have been evaluated in pancreatic acinar cells in response to H 2 O 2 , menadione, and other physiologic stimuli (Dabrowski et al, 2000).…”

Effect of NF-κB and p38 MAPK in activated monocytes/macrophages on pro-inflammatory cytokines of rats with acute pancreatitis

“…An in-vitro experiment showed that cytokine expression of acinar cells was mediated by two separate signal pathways, i.e, NF-κB and p38 MAP kinase. of which p38 MAP kinase is now suggested to play a major role [22][23][24][25][26][27] . The definitive role of these intracellular signaling cascades may lead to new designs for cytokine modulation therapy.…”