The Opposite Effect of L-kynurenine and Ahr Inhibitor Ch223191 on Apoptotic Protein Expression in Pancreatic Carcinoma Cells (Panc-1)

Leja-Szpak, Anna; Góralska, Marta; Link-Lenczowski, Paweł; Czech, Urszula; Nawrot-Porąbka, Katarzyna; Bonior, Joanna; Jaworek, Jolanta

doi:10.2174/1871520619666190415165212

Cited by 14 publications

(6 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed the same changes in proinflammatory cytokines and apoptosis‐related factors in AhR‐knockdown hGFs stimulated with Pg ‐LPS. These findings are in accordance with those of previous studies showing that AhR promotes cell proliferation and inflammation by regulating BCL2 and NF‐κB family members (Leja‐Szpak et al, 2019; Mohammadi et al, 2017; Nguyen et al, 2013). It has been noted that the activation of antiapoptotic BCL2 family members might be one of the major causes of fibrous epulis pathogenesis (Arunachalam & Rao, 2013; Jiang et al, 2020; Jung et al, 2008; Kuzenko et al, 2015; Misra et al, 2016; Saito et al, 2000; Seymour et al, 2000).…”

Section: Discussionsupporting

confidence: 93%

“…and NF-κB family members (Leja-Szpak et al, 2019;Mohammadi et al, 2017;Nguyen et al, 2013). It has been noted that the activation of antiapoptotic BCL2 family members might be one of the major causes of fibrous epulis pathogenesis (Arunachalam & Rao, 2013;Jung et al, 2008;Kuzenko et al, 2015;Misra et al, 2016;Saito et al, 2000;Seymour et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have shown that a chronic inflammatory state may active non-canonical AhR signaling pathways (e.g., by AhR binding to NF-κB, c-maf, and STATs), leading to a change in the production of cytokines or growth factors in the skin (Apetoh et al, 2010;Hollingshead et al, 2008;Kimura et al, 2008Kimura et al, , 2009Tian et al, 1999;Vogel et al, 2007) and disease development and/or persistence (Haarmann-Stemmann et al, 2015;Tauchi et al, 2005). Further, some reports have indicated that AhR, through the use of its agonists and inhibitors, may be able to modulate the proliferative and apoptotic effects of different types of cells, such as pancreatic carcinoma cells and the THP-1 monocytic cell line, through the regulation of the IDO dependent pathway and the IAPs, BCL2, and NF-κB family members (Leja-Szpak et al, 2019;Mohammadi et al, 2017). Furthermore, it is speculated that AhR plays an important role in the development of many types of tumors such as squamous cell carcinomas (He & Zhang, 2017;Hu & Zhang, 2019;Li et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

High expression of aryl hydrocarbon receptor (AhR) plays an important role in the formation of fibrous epulis

et al. 2021

View full text Add to dashboard Cite

originates from the connective tissue of the periodontal ligament and the gingiva. Though Epulis is not a true tumor, as evidenced by its non-tumor biological characteristics and structure, it can easily relapse after resection (Beaumont et al., 2017;Chesterman et al., 2017). The pathogenesis of epulis has not yet been completely delineated. Previous studies have indicated that epulis can be caused by low-grade local irritation, traumatic injury, hormonal factors, and certain drugs (Kamal et al., 2012;Punde et al., 2013). Dental plaque(bacteria) plays an important role in all forms of epulis,

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High expression of aryl hydrocarbon receptor (AhR) plays an important role in the formation of fibrous epulis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…KYN is a ligand that activates the transcriptional activity of aryl hydrocarbon receptor (AhR). We tested if AhR is required for HCMV replication using CH223191, an AhR inhibitor that blocks KYN binding (20,21). At 9 d post-treatment, DMSO-treated cells and 3 µM CH223191-treated cells had the same level of cell survival ( Figure S4).…”

Section: Ido1 and Aryl Hydrocarbon Receptor (Ahr) Activities Promote mentioning

confidence: 99%

Hypoxia-inducible factor 1α (HIF1α) Suppresses Virus Replication in Human Cytomegalovirus Infection by Limiting Kynurenine Synthesis

Wise

Purdy

2021

Preprint

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV) replication depends on the activities of several host regulators of metabolism. Hypoxia-inducible factor 1α (HIF1α) was previously proposed to support virus replication through its metabolic regulatory function. HIF1α protein levels rise in response to HCMV infection in non-hypoxic conditions, but its effect on HCMV replication was not investigated. We addressed the role of HIF1α in HCMV replication by generating primary human cells with HIF1α knocked out using CRISPR/Cas9. When HIF1α was absent, we found that HCMV replication was enhanced, showing that HIF1α suppresses viral replication. We used untargeted metabolomics to determine if HIF1α regulates metabolite concentrations in HCMV infected cells. We discovered that in HCMV-infected cells, HIF1α suppresses intracellular and extracellular concentrations of kynurenine. HIF1α also suppressed the expression of the indoleamine 2,3-dioxygenase 1 (IDO1) rate-limiting enzyme in kynurenine synthesis. In addition to its role in tryptophan metabolism, kynurenine acts as a signaling messenger by activating aryl hydrocarbon receptor (AhR). Inhibiting AhR reduces HCMV replication while activating AhR with an exogenous ligand increases HCMV replication. Moreover, we found that feeding kynurenine to cells promotes HCMV replication. Overall, our findings indicate that HIF1α reduces HCMV replication by regulating metabolism and metabolite signaling.ImportanceViruses, like human cytomegalovirus (HCMV), reprogram cellular metabolism using host metabolic regulators to support virus replication. Alternatively, in response to infection, the host can use metabolism to limit virus replication. Here, our findings show that the host uses hypoxia-inducible factor 1α (HIF1α) as a metabolic regulator to reduce HCMV replication. Further, we found that HIF1α suppresses kynurenine synthesis, a metabolite that can promote HCMV replication by signaling through the aryl hydrocarbon receptor (AhR). In infected cells, the rate-limiting enzyme in kynurenine synthesis, indoleamine 2,3-dioxygenase 1 (IDO1), is suppressed by a HIF1α-dependent mechanism. Our findings describe a functional connection between HIF1α, IDO1, and AhR that allows HIF1α to limit HCMV replication through metabolic regulation, advancing our understanding of virus-host interactions.

show abstract

“…The cytokine/IDO/kynurenine/AhR pathway is present within cancer cells, with intracellular AhR activation affording protection in cancer cells [11]. As such, an initial increased release of pro-inflammatory cytokines, especially IFNγ, from NK cells in the tumour microenvironment drives IDO induction in cancer cells, leading to intracrine kynurenine activation of the AhR that acts to protect cancer cells.…”

Section: Aryl Hydrocarbon Receptormentioning

confidence: 99%

Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

Anderson¹

2020

IJMS

View full text Add to dashboard Cite

This article reviews the dynamic interactions of the tumour microenvironment, highlighting the roles of acetyl-CoA and melatonergic pathway regulation in determining the interactions between oxidative phosphorylation (OXPHOS) and glycolysis across the array of cells forming the tumour microenvironment. Many of the factors associated with tumour progression and immune resistance, such as yin yang (YY)1 and glycogen synthase kinase (GSK)3β, regulate acetyl-CoA and the melatonergic pathway, thereby having significant impacts on the dynamic interactions of the different types of cells present in the tumour microenvironment. The association of the aryl hydrocarbon receptor (AhR) with immune suppression in the tumour microenvironment may be mediated by the AhR-induced cytochrome P450 (CYP)1b1-driven ‘backward’ conversion of melatonin to its immediate precursor N-acetylserotonin (NAS). NAS within tumours and released from tumour microenvironment cells activates the brain-derived neurotrophic factor (BDNF) receptor, TrkB, thereby increasing the survival and proliferation of cancer stem-like cells. Acetyl-CoA is a crucial co-substrate for initiation of the melatonergic pathway, as well as co-ordinating the interactions of OXPHOS and glycolysis in all cells of the tumour microenvironment. This provides a model of the tumour microenvironment that emphasises the roles of acetyl-CoA and the melatonergic pathway in shaping the dynamic intercellular metabolic interactions of the various cells within the tumour microenvironment. The potentiation of YY1 and GSK3β by O-GlcNAcylation will drive changes in metabolism in tumours and tumour microenvironment cells in association with their regulation of the melatonergic pathway. The emphasis on metabolic interactions across cell types in the tumour microenvironment provides novel future research and treatment directions.

show abstract

The Opposite Effect of L-kynurenine and Ahr Inhibitor Ch223191 on Apoptotic Protein Expression in Pancreatic Carcinoma Cells (Panc-1)

Cited by 14 publications

References 47 publications

High expression of aryl hydrocarbon receptor (AhR) plays an important role in the formation of fibrous epulis

High expression of aryl hydrocarbon receptor (AhR) plays an important role in the formation of fibrous epulis

Hypoxia-inducible factor 1α (HIF1α) Suppresses Virus Replication in Human Cytomegalovirus Infection by Limiting Kynurenine Synthesis

Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

Contact Info

Product

Resources

About