|
|
GEO help: Mouse over screen elements for information. |
|
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
|
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.
|
|
|
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).
|
|
|
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
|
Phone |
510-642-2983
|
Organization name |
Univ California-Berkeley
|
Department |
Molec/Cell Bio
|
Street address |
231 LSA
|
City |
Berkeley |
State/province |
CA |
ZIP/Postal code |
94720-3200 |
Country |
USA |
|
|
Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
Samples (6)
|
|
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 |
|
|
|
|
|