The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Unexpected link between an antibiotic, pannexin channels and apoptosis
Open accessAbstract
Plasma membrane pannexin 1 channels (PANX1) release nucleotide find-me signals from apoptotic cells to attract phagocytes. Here we show that the quinolone antibiotic trovafloxacin is a novel PANX1 inhibitor, by using a small-molecule screen. Although quinolones are widely used to treat bacterial infections, some quinolones have unexplained side effects, including deaths among children. PANX1 is a direct target of trovafloxacin at drug concentrations seen in human plasma, and its inhibition led to dysregulated fragmentation of apoptotic cells. Genetic loss of PANX1 phenocopied trovafloxacin effects, revealing a non-redundant role for pannexin channels in regulating cellular disassembly during apoptosis. Increase in drug-resistant bacteria worldwide and the dearth of new antibiotics is a major human health challenge. Comparing different quinolone antibiotics suggests that certain structural features may contribute to PANX1 blockade. These data identify a novel linkage between an antibiotic, pannexin channels and cellular integrity, and suggest that re-engineering certain quinolones might help develop newer antibacterials.
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Lakso, M., Pichel, J. G., Gorman, J. R., Sauer, B., Okamoto, Y., Lee, E., Alt, F. W., & Westphal, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5860 · Cited by 1,125
Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing
Sebbagh, M., Renvoizé, C., Hamelin, J., Riché, N., Bertoglio, J., & Bréard, J. (2001) · Nature Cell Biology · doi:10.1038/35070019 · Cited by 915
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Self-citationLiving on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology
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Self-citationThe Dynamics of Apoptotic Cell Clearance
Elliott, M. R., & Ravichandran, K. S. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.06.029 · Cited by 319
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Metadata
- Authors
- Poon, I. K. H., Chiu, Y.-H., Armstrong, A. J., Kinchen, J. M., Juncadella, I. J., Bayliss, D. A., & Ravichandran, K. S.
- Venue
- Nature
- Published
- 2014-03-12
- Volume
- 507
- Issue
- 7492
- Pages
- 329-334
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2101235551
- Cited by
- 276
- References
- 2
- FWCI
- 12.10
- Type
- journal article
- Language
- en
- Open access
- green
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- Poon, I. K. H., Chiu, Y.-H., Armstrong, A. J., Kinchen, J. M., Juncadella, I. J., Bayliss, D. A., & Ravichandran, K. S. (2014). Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature. https://doi.org/10.1038/nature13147
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