GPCR and Alcohol-Related Behaviors in Genetically Modified Mice

Neasta, Jérémie; Darcq, Emmanuel; Jeanblanc, Jérôme; Carnicella, Sébastien; Hamida, Sami Ben

doi:10.1007/s13311-019-00828-y

Cited by 10 publications

(3 citation statements)

References 409 publications

(438 reference statements)

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“…It was compelling to find the alcoholism pathway enriched. In addition to the histone genes, GNG11 (G protein subunit gamma 11) is part of the alcoholism KEGG pathway, functioning to mediate signaling in response to acute ethanol exposure [ 58 ]. There are links between GNG11 and breast cancer in the literature [ 59 ]; whether GNG11 is a molecular link between alcohol metabolism and cancer will be interesting to investigate in the future.…”

Section: Resultsmentioning

confidence: 99%

Short‐term exposure to ethanol induces transcriptional changes in nontumorigenic breast cells

et al. 2023

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Breast cancer is a leading cause of cancer‐related deaths in women. Many genetic and behavioral risk factors can contribute to the initiation and progression of breast cancer, one being alcohol consumption. Numerous epidemiological studies have established a positive correlation between alcohol consumption and breast cancer; however, the molecular basis for this link remains ill defined. Elucidating ethanol‐induced changes to global transcriptional programming in breast cells is important to ultimately understand how alcohol and breast cancer are connected mechanistically. We investigated induced transcriptional changes in response to a short cellular exposure to moderate levels of alcohol. We treated the non‐tumorigenic breast cell line MCF10A, and the tumorigenic breast cell lines MDA‐MB‐231 and MCF7, with ethanol for 6 h, then captured the changes to ongoing transcription using 4‐thiouridine metabolic labeling followed by deep sequencing. Only the MCF10A cell line exhibited statistically significant changes in newly transcribed RNA in response to ethanol treatment. Further experiments revealed that some ethanol‐upregulated genes are sensitive to the dose of alcohol treatment, while others are not. Gene ontology and biochemical pathway analyses revealed that ethanol‐upregulated genes in MCF10A cells are enriched in biological functions that could contribute to cancer development.

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Section: Resultsmentioning

confidence: 99%

Short‐term exposure to ethanol induces transcriptional changes in nontumorigenic breast cells

et al. 2023

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“…On the other hand, while low doses of 1,3-BD did not significantly increase βHB, our previous revelation that 1,3-BD can cause vasodilation of isolated resistance arteries at nanomolar concentrations (McCarthy et al, 2021), suggests that low-doses of 1,3-BD may be a health enhancing and longevity promoting independent of its metabolism into βHB. Indeed, it well known that alcohols can activate G-protein-coupled receptors (Neasta et al, 2020). Therefore, it is plausible that 1,3-BD could activate novel signaling pathways and investigation into these ketogenic-independent mechanisms are warranted.…”

Section: Discussionmentioning

confidence: 99%

Physiologic, Metabolic, and Toxicologic Profile of 1,3-Butanediol

McCarthy

Waigi

Singh

et al. 2021

J Pharmacol Exp Ther

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Ketone bodies are essential energy substrates in the absence of exogenous nutrients, and more recently, they have been suggested to prevent disease and improve longevity. βhydroxybutyrate (βHB) is the most abundant ketone body. The secondary alcohol, 1,3-butanediol (1,3-BD), is commonly administered to raise βHB bioavailability in vivo and in the absence of nutrient deprivation. However, the concentration of 1,3-BD that yields a systemic concentration of βHB similar to that observed after a 24 h fast has yet to be determined. To evaluate this knowledge gap, we administered 5%, 10%, or 20% 1,3-BD via the drinking water to adult, male Wistar-Kyoto rats for four weeks. In addition to systemic and excreted βHB concentration, physiologic, metabolic, and toxicologic parameters were measured. We report that only 20% 1,3-BD significantly elevates the systemic and urinary concentrations of βHB. Rats treated with 20% 1,3-BD had a rapid and sustained reduction in body mass. All concentrations of 1,3-BD decreased food consumption, but only the 20% concentration decreased fluid consumption.Urine volume, red blood cell count, and hematocrit suggested dehydration in the 10% and 20% 1,3-BD treated rats. Finally, 20% 1,3-BD treated rats presented with indicators of metabolic acidosis and sinusoidal dilation, but no evidence of fatty liver or hepatotoxicity. In summary, we report that 20% 1,3-BD, but not 5% or 10%, produces a systemic concentration of βHB similar to that observed after a 24 h fast. However, this concentration is associated with deleterious side effects such as body mass loss, dehydration, metabolic acidosis, and sinusoidal dilation.Significance statement: 1,3-Butanediol (1,3-BD) is often administered to stimulate the biosynthesis of the most abundant ketone body, β-hydroxybutyrate (βHB), and its purported salubrious effects. Here, we report that supra-pharmacological concentrations of 1,3-BD are This article has not been copyedited and formatted. The final version may differ from this version.

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“…Another class of proteins for which many available antagonists exist are G protein-coupled receptors (GPCR). In their review, Neasta et al focus primarily on the approach of genetic deletion or mutation of GPCR function in preclinical animal models [8]. This review covers a wide array of examples within this receptor class and the authors highlight the central role of these receptors in drug and alcohol seeking, providing support for specific candidate targets in drug development.…”

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confidence: 99%