دورية أكاديمية
A PPIX-binding probe facilitates discovery of PPIX-induced cell death modulation by peroxiredoxin
| العنوان: | A PPIX-binding probe facilitates discovery of PPIX-induced cell death modulation by peroxiredoxin |
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| المؤلفون: | Lynch, John, Wang, Yao, Li, Yuxin, Kavdia, Kanisha, Fukuda, Yu, Ranjit, Sabina, Robinson, Camenzind G., Grace, Christy R., Xia, Youlin, Peng, Junmin, Schuetz, John D. |
| المساهمون: | American Lebanese Syrian Associated Charities, U.S. Department of Health & Human Services | NIH | National Cancer Institute |
| المصدر: | Communications Biology ; volume 6, issue 1 ; ISSN 2399-3642 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous) |
| الوصف: | While heme synthesis requires the formation of a potentially lethal intermediate, protoporphyrin IX (PPIX), surprisingly little is known about the mechanism of its toxicity, aside from its phototoxicity. The cellular protein interactions of PPIX might provide insight into modulators of PPIX-induced cell death. Here we report the development of PPB, a biotin-conjugated, PPIX-probe that captures proteins capable of interacting with PPIX. Quantitative proteomics in a diverse panel of mammalian cell lines reveal a high degree of concordance for PPB-interacting proteins identified for each cell line. Most differences are quantitative, despite marked differences in PPIX formation and sensitivity. Pathway and quantitative difference analysis indicate that iron and heme metabolism proteins are prominent among PPB-bound proteins in fibroblasts, which undergo PPIX-mediated death determined to occur through ferroptosis. PPB proteomic data (available at PRIDE ProteomeXchange # PXD042631) reveal that redox proteins from PRDX family of glutathione peroxidases interact with PPIX. Targeted gene knockdown of the mitochondrial PRDX3, but not PRDX1 or 2, enhance PPIX-induced death in fibroblasts, an effect blocked by the radical-trapping antioxidant, ferrostatin-1. Increased PPIX formation and death was also observed in a T-lymphoblastoid ferrochelatase-deficient leukemia cell line, suggesting that PPIX elevation might serve as a potential strategy for killing certain leukemias. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s42003-023-05024-5 |
| الإتاحة: | https://doi.org/10.1038/s42003-023-05024-5Test https://www.nature.com/articles/s42003-023-05024-5.pdfTest https://www.nature.com/articles/s42003-023-05024-5Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.98E4970B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s42003-023-05024-5 |
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