N -(3-Oxo-acyl)-homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts
| Autor: | Chi Li, Christian Schwarzer, Terry E. Machen, Guoping Zhao, Joseph A. Burlison, Shuhan Meng, Aaron G. Whitt, Nicole S. Stivers, Aaron M. Neely |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Immunology Apoptosis Mitochondrion Microbiology Article Mice 03 medical and health sciences 4-Butyrolactone Cell Line Tumor Virology Homoserine Animals Humans Caspase Caspase 7 Mice Knockout biology Caspase 3 Effector Intrinsic apoptosis Cytochromes c Quorum Sensing Fibroblasts HCT116 Cells Molecular biology Caspase 9 Mitochondria Cell biology 030104 developmental biology Mitochondrial Membranes Pseudomonas aeruginosa biology.protein Microbial Interactions lipids (amino acids peptides and proteins) Apoptotic signaling pathway Signal transduction |
| Zdroj: | Cellular Microbiology. 20:e12787 |
| ISSN: | 1462-5814 |
| DOI: | 10.1111/cmi.12787 |
| Popis: | N-(3-Oxododecanoyl)-l-homoserine lactone (C12) is produced by Pseudomonas aeruginosa to function as a quorum-sensing molecule for bacteria-bacteria communication. C12 is also known to influence many aspects of human host cell physiology, including induction of cell death. However, the signalling pathway(s) leading to C12-triggered cell death is (are) still not completely known. To clarify cell death signalling induced by C12, we examined mouse embryonic fibroblasts deficient in "initiator" caspases or "effector" caspases. Our data indicate that C12 selectively induces the mitochondria-dependent intrinsic apoptotic pathway by quickly triggering mitochondrial outer membrane permeabilisation. Importantly, the activities of C12 to permeabilise mitochondria are independent of activation of both "initiator" and "effector" caspases. Furthermore, C12 directly induces mitochondrial outer membrane permeabilisation in vitro. Overall, our study suggests a mitochondrial apoptotic signalling pathway triggered by C12, in which C12 or its metabolite(s) acts on mitochondria to permeabilise mitochondria, leading to activation of apoptosis. |
| Databáze: | OpenAIRE |
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