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Philos Trans R Soc Lond B Biol Sci. 2016 Aug 5;371(1700). pii: 20150425. doi: 10.1098/rstb.2015.0425.

Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview.

Author information

1
First Department of Medicine, University of Szeged, Szeged, Hungary MTA-SZTE Momentum Translational Gastroenterology Research Group, University of Szeged, Szeged, Hungary.
2
First Department of Medicine, University of Szeged, Szeged, Hungary MTA-SZTE Momentum Translational Gastroenterology Research Group, University of Szeged, Szeged, Hungary Institute for Translational Medicine, University of Pécs, Pécs, Hungary hegyi.peter@pte.hu p.hegyi@tm-pte.org.

Abstract

Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30-50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca(2+) overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca(2+) signalling might be beneficial in AP. The inhibition of Ca(2+) release from the endoplasmic reticulum or the activity of plasma membrane Ca(2+) influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca(2+) homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.

KEYWORDS:

Ca2+ overload; acute pancreatitis; mitochondrial damage

PMID:
27377719
PMCID:
PMC4938025
DOI:
10.1098/rstb.2015.0425
[Indexed for MEDLINE]
Free PMC Article

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