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Ca 2+ signalling underlying pancreatitis

Gerasimenko, Julia V., Peng, Shuang, Tsugorka, Tetyana and Gerasimenko, Oleg V. 2018. Ca 2+ signalling underlying pancreatitis. Cell Calcium 70 , pp. 95-101. 10.1016/j.ceca.2017.05.010

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Abstract

In spite of significant scientific progress in recent years, acute pancreatitis (AP) is still a dangerous and in up to 5% of cases deadly disease with no specific cure. It is self-resolved in the majority of cases, but could result in chronic pancreatitis (CP) and increased risk of pancreatic cancer (PC). One of the early events in AP is premature activation of digestive pro-enzymes, including trypsinogen, inside pancreatic acinar cells (PACs) due to an excessive rise in the cytosolic Ca2+ concentration, which is the result of Ca2+ release from internal stores followed by Ca2+ entry through the store operated Ca2+ channels in the plasma membrane. The leading causes of AP are high alcohol intake and biliary disease with gallstones obstruction leading to bile reflux into the pancreatic duct. Recently attention in this area of research turned to another cause of AP – Asparaginase based drugs – which have been used quite successfully in treatments of childhood acute lymphoblastic leukaemia (ALL). Unfortunately, Asparaginase is implicated in triggering AP in 5–10% of cases as a side effect of the anti-cancer therapy. The main features of Asparaginase-elicited AP (AAP) were found to be remarkably similar to AP induced by alcohol metabolites and bile acids. Several potential therapeutic avenues in counteracting AAP have been suggested and could also be useful for dealing with AP induced by other causes. Another interesting development in this field includes recent research related to pancreatic stellate cells (PSCs) that are much less studied in their natural environment but nevertheless critically involved in AP, CP and PC. This review will attempt to evaluate developments, approaches and potential therapies for AP and discuss links to other relevant diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: Asparaginase, Pancreatic acinar cells, Pancreatic stellate cells, Acute pancreatitis, Bradykinin
Additional Information: This journal has an embargo period of 12 months (https://www.elsevier.com/journals/cell-calcium/0143-4160/open-access-options).
Publisher: Elsevier
ISSN: 0143-4160
Date of First Compliant Deposit: 19 May 2017
Date of Acceptance: 17 May 2017
Last Modified: 17 Oct 2019 17:18
URI: http://orca-mwe.cf.ac.uk/id/eprint/100709

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