Summary of Study ST002800
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001747. The data can be accessed directly via it's Project DOI: 10.21228/M8WH9J This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002800 |
| Study Title | Hepatic oxylipin profiles in mouse models of Wilson disease: new insights into early hepatic manifestations. |
| Study Summary | Hepatic inflammation is commonly identified in Wilson disease (WD), a genetic disease of hepatic and brain copper accumulation. Copper accumulation is associated with increased reactive oxygen species and activation of the non-enzymatic oxidation of membrane-bound polyunsaturated fatty acids (PUFA), with impairment of cellular structures and function. Products of PUFA oxidation are collectively known as oxylipins (OXL), which can also be produced via enzymatic pathways including lipoxygenases (LOXs), cyclooxygenases (COXs), and cytochrome P450 monooxygenases (CYPs). These bioactive lipids modulate hepatic inflammation. We aimed to examine hepatic OXLs profile at early stages of WD in mouse model of Wilson disease, the toxic milk from The Jackson Laboratory (tx-j) compared to mice with normal copper metabolism (C3H). Targeted lipidomic profiling of OXLs was performed by ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) in livers from 16 weeks old male and female mice. Hepatic OXL profiles were altered, with higher levels of PUFA alcohols, diols, and ketones. Markers of oxidative stress, 9-HETE and 9-HEPE were increased in tx-j mice. Hepatic prostaglandin and thromboxane levels in the COX pathway were increased in tx-j mice. tx-j showed altered PUFA-epoxides, suggesting altered CYP(s) activities. Our findings suggest that both non-enzymatic ROS-dependent and enzymatic PUFAs oxidation via COX and LOX pathways are associated with early stages liver disease in WD. It also indicates altered CYPs activities in animal model of WD. These novel pathways could be the target for future therapies. |
| Institute | University of California, Davis |
| Last Name | Sarode |
| First Name | Gaurav |
| Address | Genome & Biomedical Sciences Facility, 451 E. Health Sciences Dr., Davis, CA, 95616, USA |
| gsarode@ucdavis.edu | |
| Phone | 530752-6715 |
| Submit Date | 2023-07-18 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-01-18 |
| Release Version | 1 |
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Treatment:
| Treatment ID: | TR002916 |
| Treatment Summary: | NA |
