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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 14, 2015 |
| Title |
Paraoxonase 2 Serves a Proapopotic Function in Mouse and Human Cells in Response to the Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3-oxododecanoyl)-Homoserine Lactone. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKOR MEF): nuclei fragmented; mitochondrial membrane potential (∆ψmito) depolarized; Ca2+ was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca2+] (Cacyto); caspase 3/7 was activated. DKOR MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONR MEF). RNAseq analysis, qPCR and western blots showed that WT and DKOR MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), while DKONR MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONR MEF rendered them responsive to C12: ∆ψmito depolarized, Cacyto increased and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control ∆ψmito, Ca2+ release from the ER and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin, staurosporine but activates Bax- and Bak-independent apoptosis in response to C12.
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| Overall design |
Gene expression profiling of mouse embryo fibroblasts from WT and Bax/Bak double knock-out mice (C12 responsive and non-reponsive cell lines).
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| Contributor(s) |
Schwarzer C, Zu F, Morita T, Whitt AG, Neely AM, Li C, Machen TE |
| Citation(s) |
25627690 |
| Submission date |
Feb 13, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Terry E Machen |
| E-mail(s) |
tmachen@berkeley.edu
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| Phone |
510-642-2983
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| Organization name |
Univ California-Berkeley
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| Department |
Molec/Cell Bio
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| Street address |
231 LSA
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| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720-3200 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA275438 |
| SRA |
SRP055036 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE65935_DKOrvsDKOnr_diffexp.txt.gz |
963.6 Kb |
(ftp)(http) |
TXT |
| GSE65935_WTvsDKOnr_diffexp.txt.gz |
965.7 Kb |
(ftp)(http) |
TXT |
| GSE65935_WTvsDKOr_diffexp.txt.gz |
963.4 Kb |
(ftp)(http) |
TXT |
| GSE65935_normalized_readcounts.txt.gz |
686.0 Kb |
(ftp)(http) |
TXT |
| GSE65935_raw_readcounts.txt.gz |
262.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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