Differential Cytotoxicity, ER/Oxidative Stress, Dysregulated AMPKα Signaling and Mitochondrial Stress by Ethanol and its Metabolites in Human Pancreatic Acinar Cells

2021 ◽  
Author(s):  
Mukund P. Srinivasan ◽  
Kamlesh K Bhopale ◽  
Anna A Caracheo ◽  
Lata Kaphalia ◽  
Gopalakrishnan Loganathan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Mitochondrial Stress

Xanthine Oxidase-Mediated in Response to Cerulein in Intracellular Oxidative Stress Rat Pancreatic Acinar Cells

Pancreas ◽  
1993 ◽  
Vol 8 (4) ◽  
pp. 465-470 ◽  
Author(s):  
Hidekazu Suzuki ◽  
Makoto Suematsu ◽  
Soichiro Miura ◽  
Hiroshi Asako ◽  
Iwao Kurose ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Xanthine Oxidase ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Intracellular Oxidative Stress

scholarly journals Docosahexaenoic Acid Induces Expression of NAD(P)H: Quinone Oxidoreductase and Heme Oxygenase-1 through Activation of Nrf2 in Cerulein-Stimulated Pancreatic Acinar Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1084
Author(s):  
Yu Jin Ahn ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Docosahexaenoic Acid ◽  
Heme Oxygenase ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Heme Oxygenase 1 ◽  
Omega 3 ◽  
Quinone Oxidoreductase ◽  
Ar42j Cells

Oxidative stress is a major risk factor for acute pancreatitis. Reactive oxygen species (ROS) mediate expression of inflammatory cytokines such as interleukin-6 (IL-6) which reflects the severity of acute pancreatitis. The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway is activated to induce the expression of antioxidant enzymes such as NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) as a cytoprotective response to oxidative stress. In addition, binding of Kelch-like ECH-associated protein 1 (Keap1) to Nrf2 promotes degradation of Nrf2. Docosahexaenoic acid (DHA)—an omega-3 fatty acid—exerts anti-inflammatory and antioxidant effects. Oxidized omega-3 fatty acids react with Keap1 to induce Nrf2-regulated gene expression. In this study, we investigated whether DHA reduces ROS levels and inhibits IL-6 expression via Nrf2 signaling in pancreatic acinar (AR42J) cells stimulated with cerulein, as an in vitro model of acute pancreatitis. The cells were pretreated with or without DHA for 1 h and treated with cerulein (10−8 M) for 1 (ROS levels, protein levels of NQO1, HO-1, pNrf2, Nrf2, and Keap1), 6 (IL-6 mRNA expression), and 24 h (IL-6 protein level in the medium). Our results showed that DHA upregulates the expression of NQO1 and HO-1 in cerulein-stimulated AR42J cells by promoting phosphorylation and nuclear translocation of Nrf2. DHA increased interaction between Keap1 and Nrf2 in AR42J cells, which may increase Nrf2 activity by inhibiting Keap1-mediated sequestration of Nrf2. In addition, DHA-induced expression of NQO1 and HO-1 is related to reduction of ROS and IL-6 levels in cerulein-stimulated AR42J cells. In conclusion, DHA inhibits ROS-mediated IL-6 expression by upregulating Nrf2-mediated expression of NQO1 and HO-1 in cerulein-stimulated pancreatic acinar cells. DHA may exert positive modulatory effects on acute pancreatitis by inhibiting oxidative stress and inflammatory cytokine production by activating Nrf2 signaling in pancreatic acinar cells.

Role of Pancreatitis-Associated Protein 1 on Oxidative Stress-Induced Cell Death of Pancreatic Acinar Cells

2009 ◽  
Vol 1171 (1) ◽  
pp. 545-548 ◽  
Author(s):  
Joo Weon Lim ◽  
Ji Yeon Song ◽  
Jeong Yeon Seo ◽  
Hyeyoung Kim ◽  
Kyung Hwan Kim
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Pancreatitis Associated Protein

scholarly journals Oxidant-induced inhibition of the plasma membrane Ca2+-ATPase in pancreatic acinar cells: role of the mitochondria

2008 ◽  
Vol 295 (5) ◽  
pp. C1247-C1260 ◽  
Author(s):  
Erin M. Baggaley ◽  
Austin C. Elliott ◽  
Jason I. E. Bruce
Keyword(s):  
Oxidative Stress ◽  
Plasma Membrane ◽  
Cell Injury ◽  
Mitochondrial Permeability Transition ◽  
Acinar Cells ◽  
Atp Depletion ◽  
Pancreatic Acinar Cells ◽  
Spatiotemporal Pattern ◽  
Mitochondrial Depolarization

Impairment of the normal spatiotemporal pattern of intracellular Ca2+ ([Ca2+]i) signaling, and in particular, the transition to an irreversible “Ca2+ overload” response, has been implicated in various pathophysiological states. In some diseases, including pancreatitis, oxidative stress has been suggested to mediate this Ca2+ overload and the associated cell injury. We have previously demonstrated that oxidative stress with hydrogen peroxide (H2O2) evokes a Ca2+ overload response and inhibition of plasma membrane Ca2+-ATPase (PMCA) in rat pancreatic acinar cells (Bruce JI and Elliott AC. Am J Physiol Cell Physiol 293: C938–C950, 2007). The aim of the present study was to further examine this oxidant-impaired inhibition of the PMCA, focusing on the role of the mitochondria. Using a [Ca2+]i clearance assay in which mitochondrial Ca2+ uptake was blocked with Ru-360, H2O2 (50 μM–1 mM) markedly inhibited the PMCA activity. This H2O2-induced inhibition of the PMCA correlated with mitochondrial depolarization (assessed using tetramethylrhodamine methylester fluorescence) but could occur without significant ATP depletion (assessed using Magnesium Green fluorescence). The H2O2-induced PMCA inhibition was sensitive to the mitochondrial permeability transition pore (mPTP) inhibitors, cyclosporin-A and bongkrekic acid. These data suggest that oxidant-induced opening of the mPTP and mitochondrial depolarization may lead to an inhibition of the PMCA that is independent of mitochondrial Ca2+ handling and ATP depletion, and we speculate that this may involve the release of a mitochondrial factor. Such a phenomenon may be responsible for the Ca2+ overload response, and for the transition between apoptotic and necrotic cell death thought to be important in many disease states.

scholarly journals Oxidant-impaired intracellular Ca2+ signaling in pancreatic acinar cells: role of the plasma membrane Ca2+-ATPase

2007 ◽  
Vol 293 (3) ◽  
pp. C938-C950 ◽  
Author(s):  
Jason I. E. Bruce ◽  
Austin C. Elliott
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Cell Injury ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Dependent Manner ◽  
Atpase Inhibitors

Pancreatitis is an inflammatory disease of pancreatic acinar cells whereby intracellular calcium concentration ([Ca2+]i) signaling and enzyme secretion are impaired. Increased oxidative stress has been suggested to mediate the associated cell injury. The present study tested the effects of the oxidant, hydrogen peroxide, on [Ca2+]i signaling in rat pancreatic acinar cells by simultaneously imaging fura-2, to measure [Ca2+]i, and dichlorofluorescein, to measure oxidative stress. Millimolar concentrations of hydrogen peroxide increased cellular oxidative stress and irreversibly increased [Ca2+]i, which was sensitive to antioxidants and removal of external Ca2+, and ultimately led to cell lysis. Responses were also abolished by pretreatment with (sarco)endoplasmic reticulum Ca2+-ATPase inhibitors, unless cells were prestimulated with cholecystokinin to promote mitochondrial Ca2+ uptake. This suggests that hydrogen peroxide promotes Ca2+ release from the endoplasmic reticulum and the mitochondria and that it promotes Ca2+ influx. Lower concentrations of hydrogen peroxide (10–100 μM) increased [Ca2+]i and altered cholecystokinin-evoked [Ca2+]i oscillations with marked heterogeneity, the severity of which was directly related to oxidative stress, suggesting differences in cellular antioxidant capacity. These changes in [Ca2+]i also upregulated the activity of the plasma membrane Ca2+-ATPase in a Ca2+-dependent manner, whereas higher concentrations (0.1–1 mM) inactivated the plasma membrane Ca2+-ATPase. This may be important in facilitating “Ca2+ overload,” resulting in cell injury associated with pancreatitis.

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