Purinergic signalling during sterile liver injury

Oliveira, André G.; Marques, Pedro Elias; Amaral, Sylvia Stella; Quintão, Jayane L D; Cogliati, Bruno; Dagli, M.L.; Rogiers, Vera; Vanhaecke, Tamara; Vinken, Mathieu; Menezes, Gustavo B.

doi:10.1111/liv.12109

Cited by 7 publications

(6 citation statements)

References 95 publications

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“…P2Y 2 R antagonists might be useful to treat inflammatory liver disease ( Ayata et al, 2012 ). A review discusses the role of purinergic signalling in sterile liver injury ( Oliveira et al, 2013 ).…”

Section: Diseases Of the Livermentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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Section: Diseases Of the Livermentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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“…as regeneration [45], injury [46,47], ischemia/reperfusion [48], and fibrosis [10]. Thus, it is scientifically worthwhile to clarify the cell-specific distribution of the various purinergic signaling components expressed in the liver tissue.…”

Section: Ecto-nucleotidasesmentioning

confidence: 99%

Expression of mediators of purinergic signaling in human liver cell lines

Goree

Lavoie

Fausther

et al. 2014

Purinergic Signalling

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Purinergic signaling regulates a diverse and biologically relevant group of processes in the liver. However, progress of research into functions regulated by purinergic signals in the liver has been hampered by the complexity of systems probed. Specifically, there are multiple liver cell subpopulations relevant to hepatic functions, and many of these have been effectively modeled in human cell lines. Furthermore, there are more than 20 genes relevant to purinergic signaling, each of which has distinct functions. Hence, we felt the need to categorize genes relevant to purinergic signaling in the best characterized human cell line models of liver cell subpopulations. Therefore, we investigated the expression of adenosine receptor, P2X receptor, P2Y receptor, and ecto-nucleotidase genes via RT-PCR in the following cell lines: LX-2, hTERT, FH11, HepG2, Huh7, H69, and MzChA-1. We believe that our findings will provide an excellent resource to investigators seeking to define functions of purinergic signals in liver physiology and liver disease pathogenesis.

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“…In the liver, purinergic signaling is a shifting balance that greatly contributes to tissue homeostasis. 28 Under physiological conditions, intercellular purinergic signaling plays a fundamental role within hepatic lobules in several key regulatory processes including cell survival, proliferation and cell death, ion homeostasis, bile formation, glucose metabo-lism, and blood flow. 29 However, the purine-mediated signaling alteration shifts the balance toward pathological states and may influence drug-induced liver injury as a result of direct interference with drug metabolism or with cell death pathways.…”

Section: ■ Discussionmentioning

confidence: 99%

Integrated Metabolomics and Proteomics Approach To Identify Metabolic Abnormalities in Rats with Dioscorea bulbifera Rhizome-Induced Hepatotoxicity

Dong-sheng

Jiang

Wang

et al. 2018

Chem. Res. Toxicol.

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Previous studies have shown that Dioscorea bulbifera rhizome (DBR) can induce hepatotoxicity in clinical practice. However, its underlying mechanisms remain largely unexplored. In the present study, we investigated the global effect of DBR exposure on the proteomic and metabolomic profiles in rats over a 12-week administration using an integrated proteomics and metabolomics approach. The abundance of 1366 proteins and 58 metabolites in the liver of rats after subchronic exposure to DBR was dose-dependently altered. The results indicated that DBR mainly damaged hepatic cells through the aberrant regulation of multiple systems mainly including purine metabolism, pyrimidine metabolism, taurine and hypotaurine metabolism, and bile acid metabolism. Notably, the deregulated proteins including Pnp, Dpyd, Upp1, and Tymp and the differential metabolites including uridine, uracil, cytidine, thymine, adenine, adenosine, adenosine 3'-monophosphate, and deoxycytidine were well correlated to purine and pyrimidine metabolism, which might be novel pathways involved in metabolic abnormalities in rats with DBR-induced liver damage. Collectively, these findings not only contributed to understanding the mechanisms underlying the hepatotoxicity of DBR, but also illustrated the power of integrated proteomics and metabolomics approaches to improve the identification of metabolic pathways and biomarkers indicative of herb-induced liver injury.

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Purinergic signalling during sterile liver injury

Cited by 7 publications

References 95 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Expression of mediators of purinergic signaling in human liver cell lines

Integrated Metabolomics and Proteomics Approach To Identify Metabolic Abnormalities in Rats with Dioscorea bulbifera Rhizome-Induced Hepatotoxicity

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