Ethanol modifies the actin cytoskeleton in rat pancreatic acinar cells — Comparison with effects of CCK

Siegmund, E; Lüthen, Frank; Kunert, Johanna; Weber, Heike

doi:10.1159/000077023

Cited by 21 publications

(15 citation statements)

References 45 publications

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“…Acini were prepared by collagenase digestion from pancreata of female rats (150-180 g body weight) starved for 18 h as described previously (Siegmund et al 2004). Finally, the cells were suspended in Krebs-Ringer's-HEPES buffer (pH 7.4, 37°C).…”

Section: Preparation Of Pancreatic Acinimentioning

confidence: 99%

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Calpain‐mediated breakdown of cytoskeletal proteins contributes to cholecystokinin‐induced damage of rat pancreatic acini

Weber¹,

Hühns²,

Lüthen³

et al. 2009

Int J Experimental Path

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The cytosolic cysteine protease calpain is implicated in a multitude of cellular functions but also plays a role in cell damage. Our previous results suggest that an activation of calpain accompanied by a decrease in its endogenous inhibitor calpastatin may contribute to pancreatic damage during cerulein-induced acute pancreatitis. The present study aimed at the time course of secretagogue-induced calpain activation and cellular substrates of the protease. Isolated rat pancreatic acini were incubated with a supramaximal concentration of cholecystokinin (0.1 microM CCK) for 30 min in the presence or absence of the calpain inhibitor Z-Val-Phe methyl ester (100 microM ZVP). The activation of calpain and the expression of calpastatin and the actin cytoskeleton-associated proteins alphaII-spectrin, E-cadherin and vinculin were studied by immunoblotting. The cell damage was assessed by lactate dehydrogenase release and ultrastructural analysis including fluorescence-labelled actin filaments. Immediately after administration, CCK led to activation of both calpain isoforms, mu- and m-calpain. The protease activation was accompanied by a decrease in the E-cadherin level and formation of calpain-specific breakdown products of alphaII-spectrin. A calpain-specific cleavage product of vinculin appeared concomitantly with changes in the actin filament organization. No effect of CCK on calpastatin was found. Inhibition of calpain by ZVP reduced CCK-induced damage of the actin-associated proteins and the cellular ultrastructure including the actin cytoskeleton. The results suggest that CCK-induced acinar cell damage requires activation of calpain and that the actin cytoskeleton belongs to the cellular targets of the protease.

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Section: Preparation Of Pancreatic Acinimentioning

confidence: 99%

“…Fluorescence labelling of F-actin in isolated acini and confocal laser scanning microscopy F-actin labelling was performed as we have previously described (Siegmund et al 2004). Briefly, acini were fixed with 4% paraformaldehyde dissolved in HEPES buffer (in mM: 250 HEPES, 10 EGTA, and 4 MgCl 2 , pH 7.7) for 30 min.…”

Section: Electron-microscopic Evaluationmentioning

confidence: 99%

Calpain‐mediated breakdown of cytoskeletal proteins contributes to cholecystokinin‐induced damage of rat pancreatic acini

Weber¹,

Hühns²,

Lüthen³

et al. 2009

Int J Experimental Path

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“…Basal pancreatic (acinar cell) secretion has recently been reported to be inhibited in ethanol-fed rats [37] . Inhibition of pancreatic secretion due to ethanol may occur at several levels including the sphincter of Oddi (spasm) [14,15] , pancreatic ducts (protein plug formation) [5] and acinar cells (disturbances in exocytosis possibly due to acetaldehyde-induced microtubular dysfunction [38] or to ethanol-induced reorganization of F-actin in the apical cytoskeleton of acinar cells as has been described in a recent in vitro study using isolated acini [39] ). A decrease in acinar secretion may further increase the content of digestive enzymes in the cells.…”

Section: Evidence That Ethanol Administration Induces Pancreatic Injurymentioning

confidence: 99%

Molecular Mechanisms of Alcoholic Pancreatitis

Apte

Pirola

Wilson³

2005

Dig Dis

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Alcoholic pancreatitis is a major complication of alcohol abuse. Since only a minority of alcoholics develop pancreatitis, there has been a keen interest in identifying the factors that may confer individual susceptibility to the disease. Numerous possibilities have been evaluated including diet, drinking patterns and a range of inherited factors. However, at the present time, no susceptibility factor has been unequivocally identified. In contrast, considerable progress has been made with respect to the constant effects of alcohol on the pancreas. The molecular mechanisms of alcohol-induced pancreatic injury are being increasingly defined with an emphasis, in recent years, on the acinar cell itself as the principal site on ethanol-related damage. It has now been established that the acinar cell is capable of metabolizing alcohol and that the direct toxic effects of alcohol and/or its metabolites on acinar cells may predispose the gland to autodigestive injury in the presence of an appropriate triggering factor. A significant recent development relates to the characterization of pancreatic stellate cells, increasingly implicated in alcoholic pancreatic fibrosis. Here the current concepts regarding the mechanisms/pathways mediating alcohol-induced pancreatic injury are outlined.

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“…In contrast, CCK‐8 induced amylase release was significantly diminished (Lewin et al., 1984; Tachibana et al., 1996) by affecting calcium pump activity on the plama membrane (Tachibana et al., 1996). In recent studies ethanol in concentrations slightly higher than physiological concentrations (up to 87 mM) had no effect on basal amylase secretion (Gonzalez et al., 2006; Siegmund et al., 2004), whereas higher concentrations (348 mM) inhibited basal amylase secretion probably by reorganization of the actin cytoskeleton via protein kinase C activation (Siegmund et al., 2004).…”

Section: Discussionmentioning

confidence: 99%

Beer But Not Wine, Hard Liquors, or Pure Ethanol Stimulates Amylase Secretion of Rat Pancreatic Acinar Cells In Vitro

Gerloff

Singer

Feick

2009

Alcoholism Clin & Exp Res

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Our data demonstrate that beer dose-dependently increases amylase output. Since neither ethanol nor the other alcoholic beverages tested caused stimulation of amylase release, our findings indicate that nonalcoholic constituents specific for beer are responsible for this increase. These as yet unknown compounds have to be identified and considered in further studies of ethanol-induced pathological and functional changes of the pancreas.

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Ethanol modifies the actin cytoskeleton in rat pancreatic acinar cells — Comparison with effects of CCK

Cited by 21 publications

References 45 publications

Calpain‐mediated breakdown of cytoskeletal proteins contributes to cholecystokinin‐induced damage of rat pancreatic acini

Calpain‐mediated breakdown of cytoskeletal proteins contributes to cholecystokinin‐induced damage of rat pancreatic acini

Molecular Mechanisms of Alcoholic Pancreatitis

Beer But Not Wine, Hard Liquors, or Pure Ethanol Stimulates Amylase Secretion of Rat Pancreatic Acinar Cells In Vitro

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