Calcium and ATP control multiple vital functions

Petersen, O. H.; Verkhratsky, Alexei

doi:10.1098/rstb.2015.0418

Cited by 44 publications

(31 citation statements)

References 43 publications

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“…Although cells relevant to exocrine and endocrine functions of the pancreas have been extensively studied and well described in the literature (Hegyi & Petersen, ; Petersen & Verkhratsky, ), a type of pancreatic auxiliary cells was overlooked until recently. Initially observed in 1982 (Watari et al .…”

Section: Introductionmentioning

confidence: 99%

“…Although cells relevant to exocrine and endocrine functions of the pancreas have been extensively studied and well described in the literature (Hegyi & Petersen, 2013;Petersen & Verkhratsky, 2016), a type of pancreatic auxiliary cells was overlooked until recently. Initially observed in 1982 (Watari et al 1982) as vitamin A storing cells, then identified, characterised and isolated for the first time in 1998 (Apte et al 1998;Bachem et al 1998), pancreatic stellate cells (PSCs) are currently attracting interest predominantly due to their well-documented role in pancreatic fibrosis (Apte et al 2012(Apte et al , 2015.…”

Section: Introductionmentioning

confidence: 99%

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Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

Ferdek

Jakubowska

Gerasimenko

et al. 2016

The Journal of Physiology

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Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. AbstractAcute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na+‐dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca2+ and significantly reduced in the absence of Na+, showing that bile‐dependent cell death was a downstream event of Ca2+ signals. Finally, combined application of TLC‐S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC‐S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

Ferdek

Jakubowska

Gerasimenko

et al. 2016

The Journal of Physiology

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“…However, the optimal [Ca 2+ ] i , varies depending on the cell type. Cytosolic calcium effects the efficiency of ATP production via the tricarboxylic acid cycle (TCA) cycle coupled to the electron transport chain (ETC) [1–3], with transient increases of [Ca 2+ ] I stimulating mitochondrial respiration. In contrast, persistent high levels of [Ca 2+ ] i cause cellular damage leading to cell death [1].…”

Section: Introductionmentioning

confidence: 99%

An improved method for isolation of mitochondria from cell lines that enables reconstitution of calcium-dependent processes

Ishii

Beeson

et al. 2019

Analytical Biochemistry

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Optimum cytosolic calcium concentrations support balanced mitochondrial respiration. However, the concentration of cytosolic Ca2+ varies among cell types and excess cytosolic Ca2+ can cause mitochondrial dysfunction, particularly when the mitochondria are isolated from cell lines. We optimized a mitochondrial isolation protocol using a human retinal cell line to delude any excess Ca2+ and thereby minimize structural damage. We carefully measured Ca2+ uptake in part via monitoring the regulated mitochondrial soluble adenylate cyclase-protein kinase A (sAC-PKA) pathway. Here, we measured mitochondrial Ca2+-dependent PKA activity using cAMP ELISAs, and O2 consumption levels during mitochondria states II – IV with XF96e high-resolution respirometry. We found that 3 nM Ca2+ increased cAMP levels and produced optimal state III respiration. These results demonstrate that optimized isolation of mitochondria from cell lines using calcium denudation provides the best platform for the study of Ca2+-dependent regulation of mitochondrial signaling.

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“…Because Ca 2+ can interact with many potential cellular targets, signalling precision requires localized rises of the cytosolic [Ca 2+ ] ([Ca 2+ ] i ) (Petersen et al . ; Petersen & Verkhratsky, ). In the nervous system, the extremely precise control of presynaptic neurotransmitter secretion depends on close co‐localization of voltage‐gated Ca 2+ channels and the exocytotic machinery (Südhof, ).…”

Section: Introductionmentioning

confidence: 99%

Ca²⁺ tunnelling through the ER lumen as a mechanism for delivering Ca²⁺ entering via store‐operated Ca²⁺ channels to specific target sites

Petersen

Courjaret

Machaca

2017

The Journal of Physiology

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Ca2+ signalling is perhaps the most universal and versatile mechanism regulating a wide range of cellular processes. Because of the many different calcium‐binding proteins distributed throughout cells, signalling precision requires localized rises in the cytosolic Ca2+ concentration. In electrically non‐excitable cells, for example epithelial cells, this is achieved by primary release of Ca2+ from the endoplasmic reticulum via Ca2+ release channels placed close to the physiological target. Because any rise in the cytosolic Ca2+ concentration activates Ca2+ extrusion, and in order for cells not to run out of Ca2+, there is a need for compensatory Ca2+ uptake from the extracellular fluid. This Ca2+ uptake occurs through a process known as store‐operated Ca2+ entry. Ideally Ca2+ entering the cell should not diffuse to the target site through the cytosol, as this would potentially activate undesirable processes. Ca2+ tunnelling through the lumen of the endoplasmic reticulum is a mechanism for delivering Ca2+ entering via store‐operated Ca2+ channels to specific target sites, and this process has been described in considerable detail in pancreatic acinar cells and oocytes. Here we review the most important evidence and present a generalized concept.

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Calcium and ATP control multiple vital functions

Cited by 44 publications

References 43 publications

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

An improved method for isolation of mitochondria from cell lines that enables reconstitution of calcium-dependent processes

Ca²⁺ tunnelling through the ER lumen as a mechanism for delivering Ca²⁺ entering via store‐operated Ca²⁺ channels to specific target sites

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Calcium and ATP control multiple vital functions

Cited by 44 publications

References 43 publications

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

An improved method for isolation of mitochondria from cell lines that enables reconstitution of calcium-dependent processes

Ca2+ tunnelling through the ER lumen as a mechanism for delivering Ca2+ entering via store‐operated Ca2+ channels to specific target sites

Contact Info

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Resources

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Ca²⁺ tunnelling through the ER lumen as a mechanism for delivering Ca²⁺ entering via store‐operated Ca²⁺ channels to specific target sites