PXD054362
PXD054362 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Targeted depletion of renal ALKBH7 by bismuth drug prevents cisplatin-induced acute kidney injury |
| Description | Cisplatin is a potent chemotherapeutic drug widely used to treat cancers. Unfortunately, its overaccumulation in kidney proximal tubular cell (PTC) shuts down fatty acid oxidation, resulting in cell necrosis and acute kidney injury (AKI). Bismuth drugs have long been used to treat gastrointestinal tract disorder and Helicobacter pylori infection. Interestingly, bismuth drugs also mitigate cisplatin-induced AKI, but the underlying mechanism remains unknown. In this study, we found 50nM bismuth specifically reduces cisplatin-induced cell necrosis. Using multiomics and protein-small molecule interaction techniques, we identified mitochondrial protein ALKBH7 as a specific target of bismuth. And ALKBH7 is depleted upon bismuth treatment. Bismuth treatment and ALKBH7 knockdown shared a proteomic similarity in suppressing programmed necrosis and promoting fatty acid metabolism. By gene knockout and silencing, we showed ALKBH7 depletion indeed greatly mitigates cisplatin-induced cell necrosis. We further demonstrated bismuth specifically depletes renal ALKBH7, prevents cisplatin-induced AKI and greatly increases survival rate in mice. Overall, we conclude ALKBH7 is specific target of bismuth drugs, and ALKBH7 depletion suppresses cisplatin-induced PTC necrosis and prevents AKI by preserving fatty acid metabolism. |
| HostingRepository | iProX |
| AnnounceDate | 2024-07-30 |
| AnnouncementXML | Submission_2024-07-29_22:51:42.216.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Yifan Hong |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; scientific name: Mus musculus; NCBI TaxID: 10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive HF-X |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-07-29 22:50:45 | ID requested | |
| ⏵ 1 | 2024-07-29 22:51:42 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: cisplatin, acute kidney injury, bismuth, ALKBH7, necrosis |
Contact List
| Yifan Hong | |
|---|---|
| contact affiliation | Shenzhen Bay Laboratory |
| contact email | angivan@163.com |
| lab head | |
| Yifan Hong | |
| contact affiliation | Shenzhen Bay Laboratory |
| contact email | angivan@163.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
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