Aryl hydrocarbon receptor activation affects nitrergic neuronal survival and delays intestinal motility in mice

Vijay, Anitha; Boyle, Nina R.; Kumar, Supriya M; Perdew, Gary H.; Srinivasan, Shanthi; Patterson, Andrew D.

doi:10.1093/toxsci/kfad014

Cited by 3 publications

(2 citation statements)

References 66 publications

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“…Interestingly, Vijay, A. et al. found that AHR activation affects nitrergic neuronal survival and delays intestinal motility in mice ( Vijay et al., 2023 ). In brief, the AHR plays a regulatory role in intestinal motility, but the relevant mechanisms and studies are still limited and need to be further explored in the future.…”

Section: The Role Of the Aryl Hydrocarbon Receptor In Ibdmentioning

confidence: 99%

“…Recently, Zhizhu decoction has been proven to alleviate slow transit constipation by activating the AHR signaling pathway through gut microbiota (Wen et al, 2023). Interestingly, Vijay, A. et al found that AHR activation affects nitrergic neuronal survival and delays intestinal motility in mice (Vijay et al, 2023). In brief, the AHR plays a regulatory role in intestinal motility, but the relevant mechanisms and studies are still limited and need to be further explored in the future.…”

Section: Ahr In Intestinal Motilitymentioning

confidence: 99%

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Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota

Hou,

Ma,

Qin

2023

Front. Cell. Infect. Microbiol.

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Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects more than 3.5 million people, with rising prevalence. It deeply affects patients’ daily life, increasing the burden on patients, families, and society. Presently, the etiology of IBD remains incompletely clarified, while emerging evidence has demonstrated that altered gut microbiota and decreased aryl hydrocarbon receptor (AHR) activity are closely associated with IBD. Furthermore, microbial metabolites are capable of AHR activation as AHR ligands, while the AHR, in turn, affects the microbiota through various pathways. In light of the complex connection among gut microbiota, the AHR, and IBD, it is urgent to review the latest research progress in this field. In this review, we describe the role of gut microbiota and AHR activation in IBD and discussed the crosstalk between gut microbiota and the AHR in the context of IBD. Taken as a whole, we propose new therapeutic strategies targeting the AHR–microbiota axis for IBD, even for other related diseases caused by AHR-microbiota dysbiosis.

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Section: The Role Of the Aryl Hydrocarbon Receptor In Ibdmentioning

confidence: 99%

Section: Ahr In Intestinal Motilitymentioning

confidence: 99%

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota

Hou,

Ma,

Qin

2023

Front. Cell. Infect. Microbiol.

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The immunotoxicity mechanism of hemocytes in Chlamys farreri incubated with noradrenaline and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide alone or in combination

Liao,

Lei,

Zhang

et al. 2024

Fish & Shellfish Immunology

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Modulation of Ceramide-Induced Apoptosis in Enteric Neurons by Aryl Hydrocarbon Receptor Signaling: Unveiling a New Pathway beyond ER Stress

Anitha,

Kumar,

Koo

et al. 2024

IJMS

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant and a potent aryl hydrocarbon receptor (AHR) ligand, causes delayed intestinal motility and affects the survival of enteric neurons. In this study, we investigated the specific signaling pathways and molecular targets involved in TCDD-induced enteric neurotoxicity. Immortalized fetal enteric neuronal (IM-FEN) cells treated with 10 nM TCDD exhibited cytotoxicity and caspase 3/7 activation, indicating apoptosis. Increased cleaved caspase-3 expression with TCDD treatment, as assessed by immunostaining in enteric neuronal cells isolated from WT mice but not in neural crest cell-specific Ahr deletion mutant mice (Wnt1Cre+/−/Ahrb(fl/fl)), emphasized the pivotal role of AHR in this process. Importantly, the apoptosis in IM-FEN cells treated with TCDD was mediated through a ceramide-dependent pathway, independent of endoplasmic reticulum stress, as evidenced by increased ceramide synthesis and the reversal of cytotoxic effects with myriocin, a potent inhibitor of ceramide biosynthesis. We identified Sptlc2 and Smpd2 as potential gene targets of AHR in ceramide regulation by a chromatin immunoprecipitation (ChIP) assay in IM-FEN cells. Additionally, TCDD downregulated phosphorylated Akt and phosphorylated Ser9-GSK-3β levels, implicating the PI3 kinase/AKT pathway in TCDD-induced neurotoxicity. Overall, this study provides important insights into the mechanisms underlying TCDD-induced enteric neurotoxicity and identifies potential targets for the development of therapeutic interventions.

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Aryl hydrocarbon receptor activation affects nitrergic neuronal survival and delays intestinal motility in mice

Cited by 3 publications

References 66 publications

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota

The immunotoxicity mechanism of hemocytes in Chlamys farreri incubated with noradrenaline and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide alone or in combination

Modulation of Ceramide-Induced Apoptosis in Enteric Neurons by Aryl Hydrocarbon Receptor Signaling: Unveiling a New Pathway beyond ER Stress

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