Abstract：
:Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study, we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free-Ca2+ concentration ([Ca2+ ]c ), cellular oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of major mitogen-activated protein kinases were analyzed. Our results show that ebselen evoked a concentration-dependent increase in [Ca2+ ]c . The compound induced an increase in the generation of reactive oxygen species in the mitochondria. We also observed an increase in global cysteine oxidation in the presence of ebselen. In the presence of ebselen an impairment of cholecystokinin-evoked amylase release was noted. Moreover, involvement of the unfolded protein response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic translation initiation factor 2α and X-box binding protein 1 was detected. Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK in the presence of ebselen were also observed. Our results provide evidences for an impairment of cellular oxidative state and enzyme secretion, the induction of endoplasmic reticulum stress and the activation of crucial mitogen-activated protein kinases in the presence of ebselen. As a consequence ebselen exerts a potential toxic effect on AR42J cells.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Santofimia-Castaño P,Izquierdo-Alvarez A,Plaza-Davila M,Martinez-Ruiz A,Fernandez-Bermejo M,Mateos-Rodriguez JM,Salido GM,Gonzalez Adoi
10.1002/jcb.26280subject
Has Abstractpub_date
2018-01-01 00:00:00pages
1122-1133issue
1eissn
0730-2312issn
1097-4644journal_volume
119pub_type
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