Cerulein-induced acute pancreatitis is associated with c-Jun NH(2)-terminal kinase 1-dependent ferritin degradation and iron-dependent free radicals formation.
OBJECTIVE
The main goal of this work was to get insight into the mechanism of cerulein-induced reactive oxygen species (ROS) formation and impact of c-Jun NH(2)-terminal kinase (JNK) on this process.


METHODS
The study was performed on Wistar rats and on a cellular model of acute pancreatitis (AP) using AR42J cell line.


RESULTS
First of all, we observed that during AP, the iron storage protein ferritin in the rat pancreas undergoes degradation accompanied by an increased formation of protein carbonyls. Pancreatic acinar AR42J cells stimulated by cerulein showed increased labile iron pool that was accompanied by a decrease in the cellular ferritin-L level and an increase in the ROS formation. The changes in the ferritin-L level were inversely correlated with the ROS formation. The cells expressing inactive JNK1 mutant were completely resistant to cerulein-induced ferritin degradation.


CONCLUSIONS
Our data showed that cerulein-induced AP in rats and on cellular model is accompanied by JNK1-dependent ferritin degradation, increases labile iron pool and ROS formation.
From the Departments of *Emergency Medicine, †Bioenergetics and Physiology of Exercise,‡Medical Chemistry, and §Anatomy and Neurobiology, Medical University, Gdańsk, Poland; ∥Department of Molecular Biology, University of Gdańsk; and ¶Department of Biochemistry, Academy of Physical Education and Sport, Gdansk, Poland.
Maciej
M
Sledzinski
Andzelika
A
Borkowska
Alicja
A
Sielicka-Dudzin
Malgorzata
M
Halon
Michal
M
Wozniak
Jan Henryk
JH
Spodnik
Anna Herman
AH
Antosiewicz
Jedrzej
J
Antosiewicz
D000818:Animals; D002460:Cell Line; D002108:Ceruletide / Q000633:toxicity*; D005293:Ferritins / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D050505:Mutant Proteins; D017382:Reactive Oxygen Species; D002108:Ceruletide; D005293:Ferritins; D007501:Iron; D048055:Mitogen-Activated Protein Kinase 8