General Information:

Id: 4,265
Diseases: Pseudomonas aeruginosa diseases
pathogen-host system
Pseudomonas aeruginosa/mammalia
mouse embryonic fibroblasts, MEFs, challenged withN-(3-oxododecanoyl)-HSL (C12)
article
Reference: Valentine CD et al.(2013) X-Box Binding Protein 1 (XBP1s) Is a Critical Determinant of Pseudomonas aeruginosa Homoserine Lactone-Mediated Apoptosis PLoS Pathog. 9 [PMID: 23990788]

Interaction Information:

Comment Treatment of wt MEFs with C12 (N-(3-oxododecanoyl)-HSL) produced time- and dose-dependent increases in caspase 3/7 activity, similar to observations made in other cell types.
Formal Description
Interaction-ID: 43584

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

increases_activity of

gene/protein

CASP3

in mouse embryonic fibroblasts
Drugbank entries Show/Hide entries for CASP3
Comment Treatment of wt MEFs with C12 (N-(3-oxododecanoyl)-HSL) produced time- and dose-dependent increases in caspase 3/7 activity, similar to observations made in other cell types.
Formal Description
Interaction-ID: 43585

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

increases_activity of

gene/protein

CASP7

in mouse embryonic fibroblasts
Drugbank entries Show/Hide entries for CASP7
Comment The absence of the XBP1s transcription factor is responsible for reduced C12 cytotoxicity. Caspase 3/7 activation in Xbp1-/- MEFs only increased by 2-4-fold due to stimulation with 25 microM C12 (N-(3-oxododecanoyl)-HSL) for up to 8 hours or with C12 concentrations increasing to 100 microM. C12-mediated apoptosis does not require XBP1s (functional isoform) transcriptional activity.
Formal Description
Interaction-ID: 43586

gene/protein

XBP1

increases_activity of

gene/protein

CASP3

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP3
Comment The absence of the XBP1s transcription factor is responsible for reduced C12 cytotoxicity. Caspase 3/7 activation in Xbp1-/- MEFs only increased by 2-4-fold due to stimulation with 25 microM C12 (N-(3-oxododecanoyl)-HSL) for up to 8 hours or with C12 concentrations increasing to 100 microM. C12-mediated apoptosis does not require XBP1s (functional isoform) transcriptional activity.
Formal Description
Interaction-ID: 43587

gene/protein

XBP1

increases_activity of

gene/protein

CASP7

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP7
Comment According to earlier studies increased phospho-eIF2-alpha (peIF2-alpha) and phospho-p38 MAPK (p-p38 MAPK could also be detected in wt MEFs after C12 (N-(3-oxododecanoyl)-HSL) exposure for 45 minutes.
Formal Description
Interaction-ID: 43589

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

increases_phosphorylation of

gene/protein

EIF2S1

in mouse embryonic fibroblasts
Comment According to earlier studies increased phospho-eIF2-alpha (peIF2-alpha) and phospho-p38 MAPK (p-p38 MAPK could also be detected in wt MEFs after C12 (N-(3-oxododecanoyl)-HSL) exposure for 45 minutes.
Formal Description
Interaction-ID: 43590

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

increases_phosphorylation of

gene/protein

p38 MAPK

in mouse embryonic fibroblasts
Comment Both Ire1-alpha(-/-) and Xbp1(-/-) MEFs are resistant to C12 (N-(3-oxododecanoyl)-HSL) cytotoxicity. The phosphorylation of p-eIF2-alpha and p-p38 MAPK does not contribute greatly to C12-mediated cell death in MEFs. The inhibition of p38 MAPK activity (using SB203580 or SB202190) did not inhibit C12 cytotoxicity or caspase 3/7 activation in wt MEFs.
Formal Description
Interaction-ID: 43591

gene/protein

p38 MAPK

NOT increases_activity of

gene/protein

CASP3

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP3
Comment Both Ire1-alpha(-/-) and Xbp1(-/-) MEFs are resistant to C12 (N-(3-oxododecanoyl)-HSL) cytotoxicity. The phosphorylation of p-eIF2-alpha and p-p38 MAPK does not contribute greatly to C12-mediated cell death in MEFs. The inhibition of p38 MAPK activity (using SB203580 or SB202190) did not inhibit C12 cytotoxicity or caspase 3/7 activation in wt MEFs.
Formal Description
Interaction-ID: 43594

gene/protein

p38 MAPK

NOT increases_activity of

gene/protein

CASP7

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP7
Comment Both Ire1-alpha(-/-) and Xbp1(-/-) MEFs are resistant to C12 (N-(3-oxododecanoyl)-HSL) cytotoxicity. The phosphorylation of p-eIF2-alpha and p-p38 MAPK does not contribute greatly to C12-mediated cell death in MEFs. The inhibition of p38 MAPK activity (using SB203580 or SB202190) did not inhibit C12 cytotoxicity or caspase 3/7 activation in wt MEFs.
Formal Description
Interaction-ID: 43595

gene/protein

EIF2S1

NOT increases_activity of

gene/protein

CASP3

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP3
Comment Both Ire1-alpha(-/-) and Xbp1(-/-) MEFs are resistant to C12 (N-(3-oxododecanoyl)-HSL) cytotoxicity. The phosphorylation of p-eIF2-alpha and p-p38 MAPK does not contribute greatly to C12-mediated cell death in MEFs. The inhibition of p38 MAPK activity (using SB203580 or SB202190) did not inhibit C12 cytotoxicity or caspase 3/7 activation in wt MEFs.
Formal Description
Interaction-ID: 43596

gene/protein

EIF2S1

NOT increases_activity of

gene/protein

CASP7

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP7
Comment In wt MEFs, c-Jun protein levels increased by approximately two-fold after 90 minutes treatment with 25 microM C12 (N-(3-oxododecanoyl)-HSL).
Formal Description
Interaction-ID: 43598

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

increases_quantity of

gene/protein

JUN

in mouse embryonic fibroblasts
Drugbank entries Show/Hide entries for JUN
Comment Caspase 8 was also activated in C12 (N-(3-oxododecanoyl)-HSL)-stimulated MEFs.
Formal Description
Interaction-ID: 43603

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

increases_activity of

gene/protein

CASP8

in mouse embryonic fibroblasts
Comment The sensors, PERK (EIF2AK3) and IRE1-alpha (ERN1) have been associated with ER stress activated apoptotic response.
Formal Description
Interaction-ID: 43605

gene/protein

EIF2AK3

affects_activity of

Comment The sensors, PERK (EIF2AK3) and IRE1-alpha (ERN1) have been associated with ER stress activated apoptotic responses.
Formal Description
Interaction-ID: 43606

gene/protein

ERN1

affects_activity of

Drugbank entries Show/Hide entries for ERN1
Comment The sensors, PERK (EIF2AK3) and IRE1-alpha (ERN1) have been associated with ER stress activated apoptotic responses. IRE1-alpha is indirectly involved in C12-mediated cytotoxicity. C12 stimulation of cells does not significantly activate the IRE1-alpha ER stress sensor.
Formal Description
Interaction-ID: 43607

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

NOT affects_activity of

gene/protein

ERN1

in mouse embryonic fibroblasts
Drugbank entries Show/Hide entries for ERN1
Comment The sensors, PERK (EIF2AK3) and IRE1-alpha (ERN1) have been associated with ER stress activated apoptotic responses. Wild type (wt) murine embryonic fibroblasts (MEFs) and knockout MEFs, The response of Perk(-/-) MEFs to C12 was similar to that in wt MEFs indicating that C12 cytotoxicity is not dependent upon PERK activity.
Formal Description
Interaction-ID: 43608

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

NOT affects_activity of

gene/protein

EIF2AK3

in mouse embryonic fibroblasts
Comment C12 ((N-(3-oxododecanoyl)-HSL)-cytotoxicity in MEFs requires caspases (analysed Casp3/7/8) such that cell death can formally be classified as apoptosis.
Formal Description
Interaction-ID: 43609

gene/protein

CASP3

increases_activity of

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP3
Comment C12 ((N-(3-oxododecanoyl)-HSL)-cytotoxicity in MEFs requires caspases (analysed Casp3/7/8) such that cell death can formally be classified as apoptosi.
Formal Description
Interaction-ID: 43610

gene/protein

CASP7

increases_activity of

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Drugbank entries Show/Hide entries for CASP7
Comment C12 ((N-(3-oxododecanoyl)-HSL)-cytotoxicity in MEFs requires caspases (analysed Casp3/7/8) such that cell death can formally be classified as apoptosi.
Formal Description
Interaction-ID: 43611

gene/protein

CASP8

increases_activity of

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Comment During homeostatic conditions, IRE1-alpha (ERN1) RNase activity mediatse sequence specific, non-conventional splicing of a pre-mRNA (Xbp1u) to generate mature mRNA (Xbp1s) that encodes the X-box binding protein 1 transcription factor XBP1s, the functional isoform.
Formal Description
Interaction-ID: 43612

gene/protein

ERN1

affects_expression of

gene/protein

XBP1

Drugbank entries Show/Hide entries for ERN1
Comment The expression of XBP1s in XBP1s-deficient MEFs (Xbp1(-/-) or Ire1-alpha(-/-) MEFs) is sufficient to re-establish C12 mediated caspase cleavage.
Formal Description
Interaction-ID: 43613

gene/protein

XBP1

increases_activity of

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)
Comment ER stressis is known to activate intrinsic apoptosis. The P. aeruginosa-derived quorum-sensing molecule C12 (N-(3-oxododecanoyl)-HSL) is recognized by host cells and initiates stress responses including cytotoxicity.
Formal Description
Interaction-ID: 43614

increases_activity of

in mouse embryonic fibroblasts; in response to N-(3-oxododecanoyl)-HSL (C12)