Expression of mediators of purinergic signaling in human liver cell lines

Goree, Jessica R.; Lavoie, Élise G.; Fausther, Michel; Dranoff, Jonathan A.

doi:10.1007/s11302-014-9425-4

Cited by 10 publications

(8 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of each receptor isoform elicits unique responses, such that a cancer cell may benefit from increased expression of some isoforms and decreased expression of others. Confirming previous findings, P2X7, and P2Y13 expression were reduced, as compared to the other receptor isoforms, in three of the four HCC cell lines tested [ 35 , 36 ]. P2X7 purinergic receptor activation induces apoptosis by increasing intracellular levels of Ca 2+ in multiple cell types [ 10 ].…”

Section: Discussionsupporting

confidence: 88%

“…P2X3 receptor expression in afferent neurons and its role in pain sensation is well characterized [ 33 ]. Although P2X3 expression has been reported in hepatocytes, cholangiocytes, and portal vein myocyctes in the liver and liver derived cell lines, P2X3 receptor function in hepatic cells has not been well characterized [ 36 , 47 - 49 ]. Recently, P2X3 has been reported to be involved in the complex regulation of liver regeneration through its expression on Natural Killer (NK) cells [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

P2X3 purinergic receptor overexpression is associated with poor recurrence-free survival in hepatocellular carcinoma patients

et al. 2015

View full text Add to dashboard Cite

P2 purinergic receptors are overexpressed in certain cancer tissues, but the pathophysiologic relevance of purinergic signaling in hepatocellular carcinoma (HCC) remains unknown. To examine the role of P2 purinergic signaling in the pathogenesis of HCC and characterize extracellular nucleotide effects on HCC cell proliferation, two independent HCC patient cohorts were analyzed for P2 purinergic receptor expression, and nucleotide treated HCC cell lines were evaluated for effects on proliferation and cell cycle progression. Our studies suggest that multiple P2 purinergic receptor isoforms are overexpressed in liver tumors, as compared to uninvolved liver, and dysregulation of P2 purinergic receptor expression is apparent in HCC cell lines, as compared to human primary hepatocytes. High P2X3 purinergic receptor expression is associated with poor recurrence-free survival (RFS), while high P2Y13 expression is associated with improved RFS. Extracellular nucleotide treatment alone is sufficient to induce cell cycle progression, via activation of JNK signaling, and extracellular ATP-mediated activation of P2X3 receptors promotes proliferation in HCC cells. Conclusion: Our analysis of HCC patient livers and HCC cells in vitro identifies a novel role for dysregulation of P2 purinergic signaling in the induction of hyper-proliferative HCC phenotype and identifies P2X3 purinergic receptors as potential new targets for therapy.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

P2X3 purinergic receptor overexpression is associated with poor recurrence-free survival in hepatocellular carcinoma patients

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Das et al [ 133 ] demonstrated that mRNA expressions of α -SMA, collagen type 1 alpha 1 (Col1 α 1), and TGF- β 1 were significantly decreased in P2X7 gene-deleted mice compared with wild type mice, suggesting that P2X7 gene-deleted mice are protected from fibrosis. mRNA expression of P2X receptors in human LX-2, hTERT, and FH11 hepatic stellate cell lines has also been demonstrated [ 134 ].…”

Section: Fibrosismentioning

confidence: 99%

Ion Channels and Oxidative Stress as a Potential Link for the Diagnosis or Treatment of Liver Diseases

Ramírez

Vázquez-Sánchez

Carrión-Robalino

et al. 2016

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Oxidative stress results from a disturbed balance between oxidation and antioxidant systems. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) may be either harmful or beneficial to the cells. Ion channels are transmembrane proteins that participate in a large variety of cellular functions and have been implicated in the development of a variety of diseases. A significant amount of the available drugs in the market targets ion channels. These proteins have sulfhydryl groups of cysteine and methionine residues in their structure that can be targeted by ROS and RNS altering channel function including gating and conducting properties, as well as the corresponding signaling pathways associated. The regulation of ion channels by ROS has been suggested to be associated with some pathological conditions including liver diseases. This review focuses on understanding the role and the potential association of ion channels and oxidative stress in liver diseases including fibrosis, alcoholic liver disease, and cancer. The potential association between ion channels and oxidative stress conditions could be used to develop new treatments for major liver diseases.

show abstract

“…The TRL-1215 cells were grown in William's EþGlutaMax-I with penicillin/streptomycin and 10% inactivated FBS. There are reports that HepG2 and Huh7 cells do not express P2X7 mRNA (26). However, regarding HepG2 cells, this is contradicted by other data (27,28).…”

Section: Cell Culturementioning

confidence: 86%

Atorvastatin Decreases HBx-Induced Phospho-Akt in Hepatocytes via P2X Receptors

Ghalali

Martín-Renedo

Högberg

et al. 2017

Molecular Cancer Research

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer-related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol-lowering drugs, and recent epidemiologic evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes, and this rapid effect is mediated by the purinergic P2X receptors. Akt is upregulated by hepatitis viruses and has oncogenic activity in HCC; therefore, we tested the possibility that the P2X-Akt pathway is important for the anticipated anticancer effects of statins in hepatocytes. Atorvastatin decreased hepatitis B virus X protein- and insulin-induced pAkt and pGsk3β (Ser9) levels. Furthermore, Akt-induced lipogenesis was counteracted by atorvastatin, and these statin-induced effects were dependent on P2X receptors. Statin also decreased proliferation and invasiveness of hepatocytes. These data provide mechanistic evidence for a P2X receptor-dependent signaling pathway by which statins decrease pAkt, its downstream phosphorylation target pGsk3β, and lipogenesis in hepatocytes. The Akt pathway is deregulated and may act as a driver in HCC development; the P2X-Akt signaling pathway may have a role in anticancer effects of statins. .

show abstract

Expression of mediators of purinergic signaling in human liver cell lines

Cited by 10 publications

References 58 publications

P2X3 purinergic receptor overexpression is associated with poor recurrence-free survival in hepatocellular carcinoma patients

P2X3 purinergic receptor overexpression is associated with poor recurrence-free survival in hepatocellular carcinoma patients

Ion Channels and Oxidative Stress as a Potential Link for the Diagnosis or Treatment of Liver Diseases

Atorvastatin Decreases HBx-Induced Phospho-Akt in Hepatocytes via P2X Receptors

Contact Info

Product

Resources

About