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

Authors :
Gerasimenko, Julia V.
Gerasimenko, Oleg V.
Source :
Cell Calcium; Jun2023, Vol. 112, pN.PAG-N.PAG, 1p
Publication Year :
2023

Abstract

• Ca<superscript>2+</superscript> overload and ATP depletion are the main pathological processes in AP. • The CRAC channel is the most attractive therapeutic target to reduce excessive Ca<superscript>2+</superscript> entry. • Modulation of IP 3 Rs and RyRs can efficiently inhibit pathological Ca<superscript>2+</superscript> release. • Energy supplementation can effectively reduce ATP depletion in AP. 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 (Ca<superscript>2+</superscript> plateau) and significantly reduced intracellular energy (ATP depletion). These hallmarks are interdependent, i.e., Ca<superscript>2+</superscript> plateau increase energy demand for its clearance while energy production is greatly affected by the pathology. Result of long standing Ca<superscript>2+</superscript> 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 Ca<superscript>2+</superscript> overload or reduction of ATP depletion. This review will summarise these approaches, including recent developments of potential therapies for AP. [Display omitted] [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01434160
Volume :
112
Database :
Supplemental Index
Journal :
Cell Calcium
Publication Type :
Academic Journal
Accession number :
163514820
Full Text :
https://doi.org/10.1016/j.ceca.2023.102740