help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Krüger, B.
Right arrow Articles by Lerch, M. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Krüger, B.
Right arrow Articles by Lerch, M. M.
(American Journal of Pathology. 2000;157:43-50.)
© 2000 American Society for Investigative Pathology

Short Communications

The Role of Intracellular Calcium Signaling in Premature Protease Activation and the Onset of Pancreatitis

Burkhard Krüger*, Elke Albrecht* and Markus M. Lerch{dagger}

From the Division of Medical Biology,*
Institute of Pathology, University of Rostock, Rostock; and the Department of Medicine B,{dagger}
Westfälische Wilhelms-Universität, Münster, Germany

The exocrine pancreas synthesizes and secretes large amounts of digestive proteases as inactive precursor zymogens. Under physiological conditions a variety of cellular defense mechanisms protect the pancreatic acinar cell against a premature and intracellular activation of these zymogens. When these defenses fail, pancreatic autodigestion is initiated and acute pancreatitis can develop. A number of experimental observations suggest that extra- as well as intracellular calcium concentrations play an important part in the initiation of pancreatic protease activation, but the intracellular signaling events that regulate this process are unknown. Using a model system in which we used pancreatic acini (freshly prepared functional units of living acinar cells), we were able to simulate the conditions found during experimental pancreatitis in rodents. By means of a cell permeant fluorescent trypsin substrate we could demonstrate in these acini that premature protease activation is initiated at the apical acinar cell pole and occurs only in the presence of secretagogue concentrations that exceed those required for a maximum secretory response. By combining this technique with fluorescence ratio imaging for the Ca2+-sensitive dye fura-2, we could further show that this protease activation is highly dependent on the spatial as well as the temporal distribution of the corresponding Ca2+ release from stores within the same subcellular compartment and that it is not propagated to neighboring acinar cells.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. W. Michalski, F. Selvaggi, M. Bartel, T. Mitkus, A. Gorbachevski, T. Giese, P. D. Sebastiano, N. A. Giese, and H. Friess
Altered anti-inflammatory response of mononuclear cells to neuropeptide PACAP is associated with deregulation of NF-{kappa}B in chronic pancreatitis
Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G50 - G57.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. I. E. Bruce and A. C. Elliott
Oxidant-impaired intracellular Ca2+ signaling in pancreatic acinar cells: role of the plasma membrane Ca2+-ATPase
Am J Physiol Cell Physiol, September 1, 2007; 293(3): C938 - C950.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Z. Husain, W. M. Grant, F. S. Gorelick, M. H. Nathanson, and A. U. Shah
Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin
Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1594 - G1599.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
S. Wildi, J. Kleeff, J. Mayerle, A. Zimmermann, E. P Bottinger, L. Wakefield, M. W Buchler, H. Friess, and M. Korc
Suppression of transforming growth factor {beta} signalling aborts caerulein induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations
Gut, May 1, 2007; 56(5): 685 - 692.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. S. Kowalik, C. L. Johnson, S. A. Chadi, J. Y. Weston, E. N. Fazio, and C. L. Pin
Mice lacking the transcription factor Mist1 exhibit an altered stress response and increased sensitivity to caerulein-induced pancreatitis
Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1123 - G1132.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. W. Sherwood, I. A. Prior, S. G. Voronina, S. L. Barrow, J. D. Woodsmith, O. V. Gerasimenko, O. H. Petersen, and A. V. Tepikin
Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells
PNAS, March 27, 2007; 104(13): 5674 - 5679.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
L. Fischer, A. S. Gukovskaya, J. M. Penninger, O. A. Mareninova, H. Friess, I. Gukovsky, and S. J. Pandol
Phosphatidylinositol 3-kinase facilitates bile acid-induced Ca2+ responses in pancreatic acinar cells
Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G875 - G886.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
M M Lerch and W Halangk
Human pancreatitis and the role of cathepsin B.
Gut, September 1, 2006; 55(9): 1228 - 1230.
[Full Text] [PDF]

Home page
 GutHome page
S Mahurkar, M M Idris, D N Reddy, S Bhaskar, G V Rao, V Thomas, L Singh, and G R Chandak
Association of cathepsin B gene polymorphisms with tropical calcific pancreatitis
Gut, September 1, 2006; 55(9): 1270 - 1275.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. T. Hyvonen, K.-H. Herzig, R. Sinervirta, E. Albrecht, I. Nordback, J. Sand, T. A. Keinanen, J. Vepsalainen, N. Grigorenko, A. R. Khomutov, et al.
Activated Polyamine Catabolism in Acute Pancreatitis: {alpha}-Methylated Polyamine Analogues Prevent Trypsinogen Activation and Pancreatitis-Associated Mortality
Am. J. Pathol., January 1, 2006; 168(1): 115 - 122.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Z. Husain, P. Prasad, W. M. Grant, T. R. Kolodecik, M. H. Nathanson, and F. S. Gorelick
The ryanodine receptor mediates early zymogen activation in pancreatitis
PNAS, October 4, 2005; 102(40): 14386 - 14391.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
J Schnekenburger, J Mayerle, B Kruger, I Buchwalow, F U Weiss, E Albrecht, V E Samoilova, W Domschke, and M M Lerch
Protein tyrosine phosphatase {kappa} and SHP-1 are involved in the regulation of cell-cell contacts at adherens junctions in the exocrine pancreas
Gut, October 1, 2005; 54(10): 1445 - 1455.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
E. Lupia, A. Goffi, P. De Giuli, O. Azzolino, O. Bosco, E. Patrucco, M. C. Vivaldo, M. Ricca, M. P. Wymann, E. Hirsch, et al.
Ablation of Phosphoinositide 3-Kinase-{gamma} Reduces the Severity of Acute Pancreatitis
Am. J. Pathol., December 1, 2004; 165(6): 2003 - 2011.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
D C Whitcomb
Value of genetic testing in the management of pancreatitis
Gut, November 1, 2004; 53(11): 1710 - 1717.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. N. Criddle, M. G. T. Raraty, J. P. Neoptolemos, A. V. Tepikin, O. H. Petersen, and R. Sutton
Ethanol toxicity in pancreatic acinar cells: Mediation by nonoxidative fatty acid metabolites
PNAS, July 20, 2004; 101(29): 10738 - 10743.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. G. Voronina, S. L. Barrow, O. V. Gerasimenko, O. H. Petersen, and A. V. Tepikin
Effects of Secretagogues and Bile Acids on Mitochondrial Membrane Potential of Pancreatic Acinar Cells: COMPARISON OF DIFFERENT MODES OF EVALUATING {Delta}{Psi}m
J. Biol. Chem., June 25, 2004; 279(26): 27327 - 27338.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
J. H. YU, H. KIM, and K. H. KIM
Calcium-Dependent Apoptotic Gene Expression in Cerulein-Treated AR42J Cells
Ann. N.Y. Acad. Sci., December 1, 2003; 1010(1): 66 - 69.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Ch. Mooren, V. Hlouschek, T. Finkes, S. Turi, I. A. Weber, J. Singh, W. Domschke, J. Schnekenburger, B. Kruger, and M. M. Lerch
Early Changes in Pancreatic Acinar Cell Calcium Signaling after Pancreatic Duct Obstruction
J. Biol. Chem., March 7, 2003; 278(11): 9361 - 9369.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Kukor, J. Mayerle, B. Kruger, M. Toth, P. M. Steed, W. Halangk, M. M. Lerch, and M. Sahin-Toth
Presence of Cathepsin B in the Human Pancreatic Secretory Pathway and Its Role in Trypsinogen Activation during Hereditary Pancreatitis
J. Biol. Chem., June 7, 2002; 277(24): 21389 - 21396.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Simon, F. U. Weiss, M. Sahin-Toth, M. Parry, O. Nayler, B. Lenfers, J. Schnekenburger, J. Mayerle, W. Domschke, and M. M. Lerch
Hereditary Pancreatitis Caused by a Novel PRSS1 Mutation (Arg-122 right-arrow Cys) That Alters Autoactivation and Autodegradation of Cationic Trypsinogen
J. Biol. Chem., February 8, 2002; 277(7): 5404 - 5410.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
F. C. MOOREN, S. TURI, D. GUNZEL, W.-R. SCHLUE, W. DOMSCHKE, J. SINGH, and M. M. LERCH
Calcium-magnesium interactions in pancreatic acinar cells
FASEB J, March 1, 2001; 15(3): 659 - 672.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W. Halangk, B. Kruger, M. Ruthenburger, J. Sturzebecher, E. Albrecht, H. Lippert, and M. M. Lerch
Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation
Am J Physiol Gastrointest Liver Physiol, February 1, 2002; 282(2): G367 - G374.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Voronina, R. Longbottom, R. Sutton, O. H. Petersen, and A. Tepikin
Bile acids induce calcium signals in mouse pancreatic acinar cells: implications for bile-induced pancreatic pathology
J. Physiol., April 1, 2002; 540(1): 49 - 55.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the American Society for Investigative Pathology.