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• W2114485532 endingPage "2164" @default.
• W2114485532 startingPage "2156" @default.
• W2114485532 abstract "SUMMARY Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis, a disease characterised in its earliest stages by disruption of intracellular Ca2+ homeostasis. The present study was carried out in order to establish the effect of the organic pro-oxidant, tert-butylhydroperoxide (tBHP), on the mobilisation of intracellular Ca2+ stores in isolated rat pancreatic acinar cells and the mechanisms underlying this effect. Cytosolic free Ca2+ concentrations ([Ca2+]c) were monitored using a digital microspectrofluorimetric system in fura-2 loaded cells. In the presence of normal extracellular Ca2+ concentrations([Ca2+]o), perfusion of pancreatic acinar cells with 1 mmol l-1tBHP caused a slow sustained increase in[Ca2+]c. This increase was also observed in a nominally Ca2+-free medium, indicating a release of Ca2+ from intracellular stores. Pretreatment of cells with tBHP abolished the typical Ca2+ response of both the physiological agonist CCK-8 (1 nmol l-1) and thapsigargin (TPS, 1 μmol l-1), an inhibitor of the SERCA pump, in the absence of extracellular Ca2+. Similar results were observed with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP, 0.5 μmol l-1),a mitochondrial uncoupler. In addition, depletion of either agonist-sensitive Ca2+ pools by CCK-8 or TPS or mitochondrial Ca2+ pools by FCCP were unable to prevent the tBHP-induced Ca2+release. By contrast, simultaneous administration of TPS and FCCP clearly abolished the tBHP-induced Ca2+ release. These results show that tBHP releases Ca2+ from agonist-sensitive intracellular stores and from mitochondria. On the other hand, simultaneous application of FCCP and of 2-aminoethoxydiphenylborane (2-APB), a blocker of IP3-mediated Ca2+release, was unable to suppress the increase in [Ca2+]c induced by tBHP, while the application of 50 μmol l-1 of ryanodine (which is able to block the ryanodine channels) inhibits tBHP-evoked Ca2+mobilisation. These findings indicate that tBHP releases Ca2+ from non-mitochondrial Ca2+ pools through ryanodine channels." @default.
• W2114485532 created "2016-06-24" @default.
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• W2114485532 date "2006-06-01" @default.
• W2114485532 modified "2023-10-16" @default.
• W2114485532 title "Involvement of ryanodine-operated channels in<i>tert</i>-butylhydroperoxide-evoked Ca2+ mobilisation in pancreatic acinar cells" @default.
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• W2114485532 doi "https://doi.org/10.1242/jeb.02250" @default.
• W2114485532 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16709917" @default.
• W2114485532 hasPublicationYear "2006" @default.
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