The role of Ca2+ signalling in the pathology of exocrine pancreas

Gerasimenko, Julia V. ORCID: https://orcid.org/0000-0002-2262-2543 and Gerasimenko, Oleg V. ORCID: https://orcid.org/0000-0003-2573-8258 2023. The role of Ca2+ signalling in the pathology of exocrine pancreas. Cell Calcium 112 , 102740. 10.1016/j.ceca.2023.102740

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Abstract

Exocrine pancreas has been the field of many successful studies in pancreatic physiology and pathology. However, related disease - acute pancreatitis (AP) is still takes it toll with more than 100,000 related deaths worldwide per year. In spite of significant scientific progress and several human trials currently running for AP, there is still no specific treatment in the clinic. Studies of the mechanism of initiation of AP have identified two crucial conditions: sustained elevations of cytoplasmic calcium concentration (Ca2+ plateau) and significantly reduced intracellular energy (ATP depletion). These hallmarks are interdependent, i.e., Ca2+ plateau increase energy demand for its clearance while energy production is greatly affected by the pathology. Result of long standing Ca2+ plateau is destabilisation of the secretory granules and premature activation of the digestive enzymes leading to necrotic cell death. Main attempts so far to break the vicious circle of cell death have been concentrated on reduction of Ca2+ overload or reduction of ATP depletion. This review will summarise these approaches, including recent developments of potential therapies for AP.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0143-4160
Funders:	MRC
Date of First Compliant Deposit:	18 April 2023
Date of Acceptance:	6 April 2023
Last Modified:	04 Jul 2023 15:31
URI:	https://orca.cardiff.ac.uk/id/eprint/158929

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