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Mano, Ana de La; Sevillano, Sara; Dios, Isabel De; Vicente, Secundino; Manso, Manuel A.

doi:10.1023/a:1020603724002

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…Whereas the involvement of IP 3 Rs was reported previously (10, 33) the involvement of RyRs has not been investigated and is shown here for the first time.…”

Section: Bile Acids Activate Ryrs and Acidic Ca 2؉ Stores Using Cicrmentioning

confidence: 40%

“…1H). These data indicate that all Ca 2ϩ release from internal stores induced by the bile acid TLC-S occurs through the two well known intracellular Ca 2ϩ release channels, IP 3 Rs and RyRs.…”

Section: Mechanisms Of Tlc-s-inducedmentioning

confidence: 72%

“…Inhibition of IP 3 Rs and RyRs in the Acidic Store-The data presented above show that TLC-S activates both IP 3 Rs and RyRs in the ER. We have tested whether this is also the case in the acidic store using Ca 2ϩ depletion of the ER by thapsigargin and subsequent application of IP 3 R and RyR inhibitors.…”

Section: Intracellular Organelles Involved In Bile-induced Intracellumentioning

confidence: 76%

“…Simultaneous Block of both IP 3 Rs and RyRs Abolishes TLC-Sinduced Ca 2ϩ Release-We have also tested the responses to TLC-S in the presence of a combination of RyR and IP 3 R inhibitors, as shown in Fig. 1E.…”

Section: Mechanisms Of Tlc-s-inducedmentioning

confidence: 99%

“…While it is known that bile acids cause Ca 2ϩ release from the ER (12,13) and depolarization of mitochondria (20), the involvement of other organelles (32) has not been investigated. It has been shown previously that functional IP 3 Rs are needed for bile acid-induced Ca RyRs (34), controlled by cADPR or NAADP, has as yet not been studied.…”

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confidence: 99%

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Bile Acids Induce Ca2+ Release from Both the Endoplasmic Reticulum and Acidic Intracellular Calcium Stores through Activation of Inositol Trisphosphate Receptors and Ryanodine Receptors

Gerasimenko

Flowerdew

Voronina

et al. 2006

Journal of Biological Chemistry

134

138

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Gallstones can cause acute pancreatitis, an often fatal disease in which the pancreas digests itself. This is probably because of biliary reflux into the pancreatic duct and subsequent bile acid action on the acinar cells. Because Ca 2؉ toxicity is important for the cellular damage in pancreatitis, we have studied the mechanisms by which the bile acid taurolithocholic acid 3-sulfate (TLC-S) liberates Ca 2؉ . Using two-photon plasma membrane permeabilization and measurement of [Ca 2؉ ] inside intracellular stores at the cell base (dominated by ER) and near the apex (dominated by secretory granules), we have characterized the Ca 2؉ release pathways. Inhibition of inositol trisphosphate receptors (IP 3 Rs), by caffeine and 2-APB, reduced Ca 2؉ release from both the ER and an acidic pool in the granular area. Inhibition of ryanodine receptors (RyRs) by ruthenium red (RR) also reduced TLC-S induced liberation from both stores. Combined inhibition of IP 3 Rs and RyRs abolished Ca 2؉ release. RyR activation depends on receptors for nicotinic acid adenine dinucleotide phosphate (NAADP), because inactivation by a high NAADP concentration inhibited release from both stores, whereas a cyclic ADPR-ribose antagonist had no effect. Bile acid-elicited intracellular Ca 2؉ liberation from both the ER and the apical acidic stores depends on both RyRs and IP 3 Rs.Bile acids, hydrophobic derivatives of cholesterol, have been suggested as a possible cause of acute pancreatitis (1). Many patients with acute pancreatitis have gallstones, blocking the ampulla of Vater, which may allow reflux of bile into the pancreatic duct system, leading to inflammation. It has been proposed that bile acids can trigger acute pancreatitis (2-4), and they have also been postulated to be tumor promoters (5), although the mechanism of action is not clear (6). Bile salts are known to induce severe experimental pancreatitis (7-9). Recent research points mainly toward abnormal calcium signaling as a possible cause of acute pancreatitis (10 -13) while casting doubt on the originally proposed ionophore-like mechanism of action of bile acids (14,15). Previous work has shown that application of bile acids can cause an increase in the levels of cytosolic [Ca 2ϩ ] in both hepatocytes (16,17) and pancreatic acinar cells (10). Specifically, bile acids activate calcium entry into the cell and cause depletion of internal calcium stores (12). Other effects not linked to calcium signaling (18) have also been observed, including an increase in the intracellular Na ϩ concentration (19) and depolarization of the inner mitochondrial membrane (20, 21).Ca 2ϩ signaling has been extensively studied in pancreatic acinar cells (22,23) and their organelles (24 -26). They are highly polarized, with distinct basal and apical poles. The secretory granules are confined to the apical region (27), which is surrounded by a perigranular Golgi apparatus and a mitochondrial belt (28, 29). All Ca 2ϩ signals start in the apical pole, and those elicited by low agonist concentrations are most...

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“…Whereas the involvement of IP 3 Rs was reported previously (10, 33) the involvement of RyRs has not been investigated and is shown here for the first time.…”

Section: Bile Acids Activate Ryrs and Acidic Ca 2؉ Stores Using Cicrmentioning

confidence: 40%

Section: Mechanisms Of Tlc-s-inducedmentioning

confidence: 72%

Section: Intracellular Organelles Involved In Bile-induced Intracellumentioning

confidence: 76%

Section: Mechanisms Of Tlc-s-inducedmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Bile Acids Induce Ca2+ Release from Both the Endoplasmic Reticulum and Acidic Intracellular Calcium Stores through Activation of Inositol Trisphosphate Receptors and Ryanodine Receptors

Gerasimenko

Flowerdew

Voronina

et al. 2006

Journal of Biological Chemistry

134

138

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The anatomical study on the rat pancreas and its ducts with emphasis on the surgical approach

Kara

2005

Annals of Anatomy - Anatomischer Anzeiger

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Changes in the expression and dynamics of SHP-1 and SHP-2 during cerulein-induced acute pancreatitis in rats

Sarmiento

Sánchez-Bernal²,

Ayra³

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Protein tyrosine phosphatases (PTPs) are important regulators of cell functions but data on different PTP expression and dynamics in acute pancreatitis (AP) are very scarce. Additionally, both c-Jun N-terminal kinases (JNK) and extracellular signal-regulated kinases (ERK1/2), together with intracellular cAMP levels in inflammatory cells, play an essential role in AP. In this study we have detected an increase in PTP SHP-1 and SHP-2 in the pancreas at the level of both protein and mRNA as an early event during the development of Cerulein (Cer)-induced AP in rats. Nevertheless, while SHP-2 protein returned to baseline levels in the intermediate or later phases of AP, SHP-1 protein expression remained increased throughout the development of the disease. The increase in SHP-2 protein expression was associated with changes in its subcellular distribution, with higher percentages located in the fractions enriched in lysosomes+mitochondria or microsomes. Furthermore, while the increase in SHP-2 protein was also observed in sodium-taurocholate duct infusion or bile-pancreatic duct obstruction AP, that of SHP-1 was specific to the Cer-induced model. Neutrophil infiltration did not affect the increase in SHP-1 protein, but favoured the return of SHP-2 protein to control levels, as indicated when rats were rendered neutropenic by the administration of vinblastine sulfate. Inhibition of JNK and ERK1/2 with SP600125 pre-treatment further increased the expression of both SHP-1 and SHP-2 proteins in the early phase of Cer-induced AP, while the inhibition of type IV phosphodiesterase with rolipram only suppressed the increase in SHP-2 protein expression during the same phase. Our results show that AP is associated with increases in the expression of SHP-1 and SHP-2 and changes in the dynamics of SHP-2 subcellular distribution in the early phase of Cer-induced AP. Finally, both JNK and ERK1/2 and intracellular cAMP levels are able to modulate the expression of these PTPs.

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Untitled

Cited by 8 publications

References 26 publications

Bile Acids Induce Ca2+ Release from Both the Endoplasmic Reticulum and Acidic Intracellular Calcium Stores through Activation of Inositol Trisphosphate Receptors and Ryanodine Receptors

Bile Acids Induce Ca2+ Release from Both the Endoplasmic Reticulum and Acidic Intracellular Calcium Stores through Activation of Inositol Trisphosphate Receptors and Ryanodine Receptors

The anatomical study on the rat pancreas and its ducts with emphasis on the surgical approach

Changes in the expression and dynamics of SHP-1 and SHP-2 during cerulein-induced acute pancreatitis in rats

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