PXD019505 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Toxicoproteomic Profiling of hPXR Transgenic Mice Treated with Rifampicin and Isoniazid |
Description | Tuberculosis is a global health threat that affects millions of people every year, and treatment-limiting toxicity remains a considerable source of treatment failure. Recent reports have characterized the nature of hPXR-mediated hepatotoxicity and systemic toxicity of antitubercular drugs. The antitubercular drug isoniazid plays a role in such pathologic states as acute intermittent porphyria, anemia, hepatotoxicity, hypercoagulable states (deep vein thrombosis, pulmonary embolism, or ischemic stroke), pellagra (vitamin B3 deficiency), peripheral neuropathy, and vitamin B6 deficiency. However, the mechanisms by which isoniazid administration leads to these states are unclear. To elucidate the mechanism of rifampicin- and isoniazid-induced liver and systemic injury, we performed tandem mass tag mass spectrometry-based proteomic screening of mPxr–/– and hPXR mice treated with combinations of rifampicin and isoniazid. Proteomic profiling analysis suggested that the hPXR liver proteome is affected by antitubercular therapy to disrupt [Fe–S] cluster assembly machinery, [2Fe–2S] cluster-containing proteins, CYP450 enzymes, heme biosynthesis, homocysteine catabolism, oxidative stress responses, vitamin B3 metabolism, and vitamin B6 metabolism. These findings provide insight into the etiology of some of these processes and potential targets for subsequent investigations. |
HostingRepository | PRIDE |
AnnounceDate | 2020-07-19 |
AnnouncementXML | Submission_2020-07-18_18:37:05.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Trent Brewer |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-06-01 18:25:52 | ID requested | |
⏵ 1 | 2020-07-18 18:37:06 | announced | |
Publication List
Brewer CT, Kodali K, Wu J, Shaw TI, Peng J, Chen T, Transgenic Mice Treated with Rifampicin and Isoniazid. Cells, 9(7):(2020) [pubmed] |
Keyword List
submitter keyword: anemia |
antitubercular therapy |
cytochrome P450 |
drug-induced liver injury |
heme biosynthesis |
hypercoagulability |
iron–sulfur cluster |
pellagra |
vitamin B3 |
vitamin B6 |
Contact List
Taosheng Chen |
contact affiliation | High-Throughput Biological Sciences, Department of Chembical Biology & Therapeutics, St. Jude Children's Research Hospital |
contact email | Taosheng.chen@stjude.org |
lab head | |
Trent Brewer |
contact affiliation | UTHSC |
contact email | cbrewe16@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD019505 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019505
- Label: PRIDE project
- Name: Toxicoproteomic Profiling of hPXR Transgenic Mice Treated with Rifampicin and Isoniazid