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Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation

Jakubowska, Monika A., Ferdek, Pawel E., Gerasimenko, Oleg V. ORCID:, Gerasimenko, Julia V. ORCID: and Petersen, Ole H. ORCID: 2016. Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation. Open Biology 6 (8) , 160149. 10.1098/rsob.160149

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The mammalian diffuse stellate cell system comprises retinoid-storing cells capable of remarkable transformations from a quiescent to an activated myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract attention owing to the pivotal role they play in development of tissue fibrosis in chronic pancreatitis and pancreatic cancer. However, little is known about the actual role of PSCs in the normal pancreas. These enigmatic cells have recently been shown to respond to physiological stimuli in a manner that is markedly different from their neighbouring pancreatic acinar cells (PACs). Here, we demonstrate the capacity of PSCs to generate nitric oxide (NO), a free radical messenger mediating, for example, inflammation and vasodilatation. We show that production of cytosolic NO in PSCs is unambiguously related to cytosolic Ca2+ signals. Only stimuli that evoke Ca2+ signals in the PSCs elicit consequent NO generation. We provide fresh evidence for the striking difference between signalling pathways in PSCs and adjacent PACs, because PSCs, in contrast to PACs, generate substantial Ca2+-mediated and NOS-dependent NO signals. We also show that inhibition of NO generation protects both PSCs and PACs from necrosis. Our results highlight the interplay between Ca2+ and NO signalling pathways in cell–cell communication, and also identify a potential therapeutic target for anti-inflammatory therapies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: calcium; inflammation; nitric oxide; pancreas; stellate cell
Additional Information: Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited.
Publisher: The Royal Society
ISSN: 2046-2441
Date of First Compliant Deposit: 9 August 2016
Date of Acceptance: 5 July 2016
Last Modified: 06 May 2023 04:54

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