PXD019505-1

PXD019505 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-01 18:25:52	ID requested
⏵ 1	2020-07-18 18:37:06	announced

Brewer CT, Kodali K, Wu J, Shaw TI, Peng J, Chen T, Transgenic Mice Treated with Rifampicin and Isoniazid. Cells, 9(7):(2020) [pubmed]

submitter keyword: anemia

antitubercular therapy

cytochrome P450

drug-induced liver injury

heme biosynthesis

hypercoagulability

iron–sulfur cluster

pellagra

vitamin B3

vitamin B6

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

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PRIDE project URI

• PRIDE
  1. PXD019505
     1. Label: PRIDE project
     2. Name: Toxicoproteomic Profiling of hPXR Transgenic Mice Treated with Rifampicin and Isoniazid