Characterization of the Tissue Distribution of the Mouse<i>Cyp2c</i>Subfamily by Quantitative PCR Analysis

Graves, Joan P.; Gruzdev, Artiom; Bradbury, J. Alyce; DeGraff, Laura M.; Edin, Matthew L.; Zeldin, Darryl C.

doi:10.1124/dmd.117.075697

Cited by 26 publications

(20 citation statements)

References 40 publications

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“…We then proceeded to investigate the the interactions of AEA and the eVDs at the enzymological level to gain better molecular insight into the metabolism. CYP2J9, CYP2J12, and CYP2J2 were all shown to be highly expressed in mouse and human brains 43 , 44 , 57 – 59 . Additionally, CYPs such as CYP2J6 are expressed in DRGs and is involved in the epoxidation of lipids that act on TRPV1 when paclitaxel is administered.…”

Section: Discussionmentioning

confidence: 98%

Anti-inflammatory dopamine- and serotonin-based endocannabinoid epoxides reciprocally regulate cannabinoid receptors and the TRPV1 channel

et al. 2021

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The endocannabinoid system is a promising target to mitigate pain as the endocannabinoids are endogenous ligands of the pain-mediating receptors—cannabinoid receptors 1 and 2 (CB1 and CB2) and TRPV1. Herein, we report on a class of lipids formed by the epoxidation of N-arachidonoyl-dopamine (NADA) and N-arachidonoyl-serotonin (NA5HT) by epoxygenases. EpoNADA and epoNA5HT are dual-functional rheostat modulators of the endocannabinoid-TRPV1 axis. EpoNADA and epoNA5HT are stronger modulators of TRPV1 than either NADA or NA5HT, and epoNA5HT displays a significantly stronger inhibition on TRPV1-mediated responses in primary afferent neurons. Moreover, epoNA5HT is a full CB1 agonist. These epoxides reduce the pro-inflammatory biomarkers IL-6, IL-1β, TNF-α and nitrous oxide and raise anti-inflammatory IL-10 cytokine in activated microglial cells. The epoxides are spontaneously generated by activated microglia cells and their formation is potentiated in the presence of anandamide. Detailed kinetics and molecular dynamics simulation studies provide evidence for this potentiation using the epoxygenase human CYP2J2. Taken together, inflammation leads to an increase in the metabolism of NADA, NA5HT and other eCBs by epoxygenases to form the corresponding epoxides. The epoxide metabolites are bioactive lipids that are potent, multi-faceted molecules, capable of influencing the activity of CB1, CB2 and TRPV1 receptors.

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Section: Discussionmentioning

confidence: 98%

Anti-inflammatory dopamine- and serotonin-based endocannabinoid epoxides reciprocally regulate cannabinoid receptors and the TRPV1 channel

et al. 2021

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“…4b ). For example, SiGra realizes remarkable enhancement of hepatocyte’s hallmark genes Cyp2c38 31 and Axin2 32 , which are predominantly expressed near blood vessels. The endothelial cell markers Cd34 33 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

SiGra: Single-cell spatial elucidation through image-augmented graph transformer

Tang

Zhang

Yang

et al. 2022

Preprint

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The recent advances in high throughput molecular imaging push the spatial transcriptomics technologies to the subcellular resolution, which breaks the limitations of both single cell RNA seq and array based spatial profiling. The latest released single cell spatial transcriptomics data from NanoString CosMx and MERSCOPE platforms contains multi channel immunohistochemistry images with rich information of cell types, functions, and morphologies of cellular compartments. In this work, we developed a novel method, Single cell spatial elucidation through image augmented Graph transformer (SiGra), to reveal spatial domains and enhance the substantially sparse and noisy transcriptomics data. SiGra applies hybrid graph transformers over a spatial graph that comprises high-content images and gene expressions of individual cells. SiGra outperformed state of the art methods on both single cell spatial profiles and spot level spatial transcriptomics data from complex tissues. The inclusion of immunohistochemistry images improved the model performance by 37% (95%CI: 27% to 50%). SiGra improves the characterization of intratumor heterogeneity and intercellular communications in human lung cancer samples, meanwhile recovers the known microscopic anatomy in both human brain and mouse liver tissues. Overall, SiGra effectively integrates different spatial modality data to gain deep insights into the spatial cellular ecosystems.

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“…The copyright holder for this preprint (which this version posted May 10, 2021. ; https://doi.org/10.1101/2021.05.10.443487 doi: bioRxiv preprint 20 contribute to the liver damage phenotypes in the Cyp2c -/mice as others have suggested [30]. Because Cyp2c enzymes are also involved in drug metabolism and detoxifying xenobiotics [41,42], we cannot rule out that these roles also contribute to the effects of Cyp2c deletion on liver damage.…”

Section: Discussionmentioning

confidence: 96%

Absence of muricholic acid due to Cyp2c-deficiency protects against high fat diet-induced obesity in male mice but promotes liver damage

Oteng

Higuchi

Banks

et al. 2021

Preprint

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Objective: Murine-specific muricholic acids (MCAs) are reported to protect against obesity and associated metabolic disorders. However, the response of mice with genetic depletion of MCA to an obesogenic diet has not been evaluated. We used Cyp2c-deficient (Cyp2c-/-) mice, which lack MCAs and thus have a human-like bile acid (BA) profile, to directly investigate the potential role of MCAs in diet-induced obesity. Methods: Male and female Cyp2c-/- mice and wild-type controls were fed a standard chow diet or a high fat diet (HFD) for 18 weeks. We measured BA composition from a pool of liver, gallbladder, and intestine, as well as weekly body weight, food intake, lean and fat mass, systemic glucose homeostasis, energy expenditure, intestinal lipid absorption, fecal lipid, and energy content. Results: Cyp2c deficiency depleted MCAs and caused other changes in BA composition, namely a decrease in the ratio of 12α-hydroxylated (12α-OH) BAs to non-12α-OH BAs, without altering the total BA levels. While wild-type male mice became obese after HFD-feeding, Cyp2c-/- male mice were protected from obesity and associated metabolic dysfunctions. Cyp2c-/- male mice also showed reduced intestinal lipid absorption and increased lipid excretion, which was reversed by oral gavage with the 12α-OH BA, taurocholic acid. Cyp2c-/- mice also showed increased liver damage, which appeared stronger in females. Conclusion: MCA does not protect against diet-induced obesity but may protect against liver injury. Reduced lipid absorption in Cyp2c-deficient male mice is potentially due to a reduced ratio of 12α-OH/non-12α-OH BAs.

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Characterization of the Tissue Distribution of the MouseCyp2cSubfamily by Quantitative PCR Analysis

Cited by 26 publications

References 40 publications

Anti-inflammatory dopamine- and serotonin-based endocannabinoid epoxides reciprocally regulate cannabinoid receptors and the TRPV1 channel

Anti-inflammatory dopamine- and serotonin-based endocannabinoid epoxides reciprocally regulate cannabinoid receptors and the TRPV1 channel

SiGra: Single-cell spatial elucidation through image-augmented graph transformer

Absence of muricholic acid due to Cyp2c-deficiency protects against high fat diet-induced obesity in male mice but promotes liver damage

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