PXD005434

PXD005434 is an original dataset announced via ProteomeXchange.

Title	mouse liver kidney LC-MS/MS
Description	Triptolide (TP), the major active component in Tripterygium wilfordii Hook. f. (Tripterygium Glycosides), contributes to treat rheumatoid arthritis and anticancer activities. However, the organ toxicity, especially nephrotoxicity and hepatotoxicity limit its clinical application. To fully understand the mechanism underlying the triptolide induced toxicity, iTRAQ based proteomics and targeted fatty acids analysis were performed. In the present study, mouse were treated with LD50 dose of triptolide, and plasma, liver and kidney tissues were harvested before drug administration (0 h) and after drug administration (0.5 h, 1 h, 2 h, 8 h, 16 h). The blood biochemical levels (ALT, AST, BUN and CRE) were used to evaluated the toxicity of triptolide. 2D-LC-MS/MS approach was used to compare different proteins among groups 0h, 1h, 2h and 8 h. Functional annotation of different proteins in liver between different groups reveals that the top 3 pathways influenced by the TP were acute phase response signaling, antigen presentation pathway and FXR/RXR activation, the molecular and cellular functions which was mainly effected were lipid metabolism and small molecule biochemistry. In kidney, the pathway including LPS/IL-1 Mediated Inhibition of RXR Function, EIF2 Signaling, acute phase response signaling, and LXR/RXR Activation were mainly affected. The proteomics data implicated that fatty acids (FAs) may involve in the organ toxicity induced by TP. Then targeted fatty acids analysis was carried out to determinate the concentration between the different groups (0.5 h, 1 h, 2 h, 8 h, 16 h) by HPLC-MRM. We found that fatty acids in liver (C17:0, C18:0, C18:2, C18:3, C20:0, C20:3, C20:4, C22:1, C22:2, C22:3, C22:4, C22:5, C22:6, C24:0, C24:1, C24:2, C24:3, C24:4, C24:5, C24:6) show significant difference among groups, while in kidney, FAs (C12:0, C12:1, C14:0, C14:1, C16:1, C16:2) show significant difference. P450 protein family show significant change in different group, protein CYP4A14 demonstrate change in both kidney and liver tissues. By combing proteomics and targeted FAs analysis, we deeply investigated the mechanism underlying the TP induced organ toxicity, and the results may provide deeply insight into prevention or intervention in the TP clinical usage and improving its safety.
HostingRepository	PRIDE
AnnounceDate	2018-07-05
AnnouncementXML	Submission_2018-07-05_05:32:29.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD005434
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Menglin Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ4plex; Oxidation; Carbamidomethyl
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-11-24 01:01:10	ID requested
⏵ 1	2018-07-05 05:32:31	announced

Li M, Hu T, Tie C, Qu L, Zheng H, Zhang J, Quantitative Proteomics and Targeted Fatty Acids Analysis Reveal the Damage of Triptolide in Liver and Kidney. Proteomics, 17(22):(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Triptolide

Proteomics

Kidney

Liver

Fatty Acids

2D-LC-MS/MS

Organ Toxicity

Jinlan Zhang
contact affiliation	State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
contact email	zhjl@imm.ac.cn
lab head
Menglin Li
contact affiliation	Peking Union Medical College
contact email	menglinli86@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005434
     1. Label: PRIDE project
     2. Name: mouse liver kidney LC-MS/MS