Thimerosal modulates the agonist‐specific cytosolic Ca<sup>2+</sup> oscillatory patterns in single pancreatic acinar cells of mouse

Wu, Jie; Takeo, Teruko; Kamimura, Noritaka; Wada, J.; Suga, Sechiko; Hoshina, Y; Wakui, Makoto

doi:10.1016/0014-5793(96)00646-1

Cited by 19 publications

(20 citation statements)

References 32 publications

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“…Regarding the main channels for calcium release from internal stores, thiol oxidants acting on sulfydryl residues release calcium through IP 3 R (5, 7, 52) and RyR (1,23,80), a mechanism that enhances (and even elicits) Ca 2ϩ oscillations in exocrine cells (81,90) and HeLa cells (5). This process could be due to sensitization of IP 3 R-mediated calcium release (51,52) to resting IP 3 levels, a phenomenon that has been integrated in a model to facilitate calcium oscillations (52).…”

Section: Mitochondrial Production Of Reactive Oxygen Speciesmentioning

confidence: 99%

Mitochondrial reactive oxygen species and Ca²⁺ signaling

Camello-Almaraz

Gomez‐Pinilla²,

Pozo³

et al. 2006

American Journal of Physiology-Cell Physiology

283

194

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Mitochondria are an important source of reactive oxygen species (ROS) formed as a side product of oxidative phosphorylation. The main sites of oxidant production are complex I and complex III, where electrons flowing from reduced substrates are occasionally transferred to oxygen to form superoxide anion and derived products. These highly reactive compounds have a well-known role in pathological states and in some cellular responses. However, although their link with Ca2+ is well studied in cell death, it has been hardly investigated in normal cytosolic calcium concentration ([Ca2+]i) signals. Several Ca2+ transport systems are modulated by oxidation. Oxidation increases the activity of inositol 1,4,5-trisphosphate and ryanodine receptors, the main channels releasing Ca2+ from intracellular stores in response to cellular stimulation. On the other hand, mitochondria are known to control [Ca2+]i signals by Ca2+ uptake and release during cytosolic calcium mobilization, specially in mitochondria situated close to Ca2+ release channels. Mitochondrial inhibitors modify calcium signals in numerous cell types, including oscillations evoked by physiological stimulus. Although these inhibitors reduce mitochondrial Ca2+ uptake, they also impair ROS production in several systems. In keeping with this effect, recent reports show that antioxidants or oxidant scavengers also inhibit physiological calcium signals. Furthermore, there is evidence that mitochondria generate ROS in response to cell stimulation, an effect suppressed by mitochondrial inhibitors that simultaneously block [Ca2+]i signals. Together, the data reviewed here indicate that Ca2+-mobilizing stimulus generates mitochondrial ROS, which, in turn, facilitate [Ca2+]i signals, a new aspect in the biology of mitochondria. Finally, the potential implications for biological modeling are discussed.

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Section: Mitochondrial Production Of Reactive Oxygen Speciesmentioning

confidence: 99%

Mitochondrial reactive oxygen species and Ca²⁺ signaling

Camello-Almaraz

Gomez‐Pinilla²,

Pozo³

et al. 2006

American Journal of Physiology-Cell Physiology

283

194

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“…Patch-clamp, whole-cell recording Ca 2+ -activated Cl -currents were recorded using conventional whole-cell recordings to monitor intracellular Ca 2+ signal oscillations as previously reported [17][18][19] . When the recording pipette was filled with the K + -containing pipette solution, the resistance was 3-4 MΩ.…”

Section: Methodsmentioning

confidence: 99%

“…Acutely dissociated mouse pancreatic acinar cells Single pancreatic acinar cells were dissociated as previously described [17][18][19] . Briefly, adult (4-6 months old) male CD1 mice were anesthetized with isoflurane, and then the pancreas was rapidly removed and injected with collagenase (200 U/mL) dissolved in standard extracellular solution(see below).…”

Section: Methodsmentioning

confidence: 99%

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

et al. 2014

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Aim: Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca 2+ oscillations in mouse pancreatic acinar cells in vitro. Methods: Acutely dissociated pancreatic acinar cells of mice were prepared. A U-tube drug application system was used to deliver drugs into the bath. Intracellular Ca 2+ oscillations were monitored by whole-cell recording of Ca 2+ -activated Cl -currents and by using confocal Ca 2+ imaging. For intracellular drug application, the drug was added in pipette solution and diffused into cell after the wholecell configuration was established. Results: Bath application of ACh (10 nmol/L) induced typical Ca 2+ oscillations in dissociated pancreatic acinar cells. Addition of congo red (1, 10, 100 µmol/L) dose-dependently enhanced Ach-induced Ca 2+ oscillations, but congo red alone did not induce any detectable response. Furthermore, this enhancement depended on the concentrations of ACh: congo red markedly enhanced the Ca 2+ oscillations induced by ACh (10-30 nmol/L), but did not alter the Ca 2+ oscillations induced by ACh (100-10000 nmol/L). Congo red also enhanced the Ca 2+ oscillations induced by bath application of IP 3 (30 µmol/L). Intracellular application of congo red failed to alter ACh-induced Ca 2+ oscillations. Conclusion: Congo red significantly modulates intracellular Ca 2+ signaling in pancreatic acinar cells, and this pharmacological effect should be fully considered when developing congo red as a novel therapeutic drug.

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“…In fact, it has been reported that other oxidising agents, like H 2 O 2 , release Ca 2+ from intracellular stores by activation of the ryanodine receptor (Favero et al, 1995;Oba et al, 1998) and that sulphydryl groups (susceptible to oxidation) have a critical role in the ryanodine-sensitive Ca 2+ channel (Oba et al, 1998). In addition, ryanodine shows 'in vitro' sensitisation in the presence of the sulphydryl group oxidising agent thimerosal (Abramson et al, 1995;Wu et al, 1996).…”

Section: Inmentioning

confidence: 99%

Involvement of ryanodine-operated channels intert-butylhydroperoxide-evoked Ca2+ mobilisation in pancreatic acinar cells

Martinez-Burgos

Granados

González

et al. 2006

Journal of Experimental Biology

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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.

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Thimerosal modulates the agonist‐specific cytosolic Ca²⁺ oscillatory patterns in single pancreatic acinar cells of mouse

Cited by 19 publications

References 32 publications

Mitochondrial reactive oxygen species and Ca²⁺ signaling

Mitochondrial reactive oxygen species and Ca²⁺ signaling

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

Involvement of ryanodine-operated channels intert-butylhydroperoxide-evoked Ca2+ mobilisation in pancreatic acinar cells

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Thimerosal modulates the agonist‐specific cytosolic Ca2+ oscillatory patterns in single pancreatic acinar cells of mouse

Cited by 19 publications

References 32 publications

Mitochondrial reactive oxygen species and Ca2+ signaling

Mitochondrial reactive oxygen species and Ca2+ signaling

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

Involvement of ryanodine-operated channels intert-butylhydroperoxide-evoked Ca2+ mobilisation in pancreatic acinar cells

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Thimerosal modulates the agonist‐specific cytosolic Ca²⁺ oscillatory patterns in single pancreatic acinar cells of mouse

Mitochondrial reactive oxygen species and Ca²⁺ signaling

Mitochondrial reactive oxygen species and Ca²⁺ signaling