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Series GSE65935 Query DataSets for GSE65935
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
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)
GSM1611440 WT_MEF1
GSM1611441 WT_MEF2
GSM1611442 DKOR_MEF1
BioProject PRJNA275438
SRA SRP055036

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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
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Raw data are available in SRA

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