General Information:

Id: 1,086
Diseases: Parkinson disease
Mus musculus
BTO:0000099 astrocyte
article
Reference: Waak J et al.(2009) Regulation of astrocyte inflammatory responses by the Parkinsons disease-associated gene DJ-1 FASEB J. 23: 2478-2489 [PMID: 19276172]

Interaction Information:

Comment Bacterial endotoxin LPS triggers neuroinflammatory response in astrocytes.
Formal Description
Interaction-ID: 6884

drug/chemical compound

Lipopolysaccharide

increases_activity of

process

inflammatory response

in astrocytes
Comment ICAM-1 is highly expressed in reactive astrocytes in brain of PD patients.
Formal Description
Interaction-ID: 6885

disease

Parkinson disease

increases_quantity of

gene/protein

ICAM1

Drugbank entries Show/Hide entries for ICAM1
Comment LPS induced ICAM-1 expression on both Dj-1+/+ and Dj-1-/- astrocytes.
Formal Description
Interaction-ID: 6886

drug/chemical compound

Lipopolysaccharide

increases_expression of

gene/protein

ICAM1

in astrocytes
Drugbank entries Show/Hide entries for ICAM1
Comment Dj-1-/- astrocytes produced 10 times more NO in response to LPS compared with wild-type controls and reverted to wild-type levels after transduction of DJ-1.
Formal Description
Interaction-ID: 6887

gene/protein

PARK7

decreases_quantity of

drug/chemical compound

NO

in response to LPS, via p38MAPK pathway
Drugbank entries Show/Hide entries for PARK7
Comment LPS signaling is mediated via TLR4.
Formal Description
Interaction-ID: 6888

gene/protein

TLR4

affects_activity of

drug/chemical compound

Lipopolysaccharide

Drugbank entries Show/Hide entries for TLR4
Comment LPS signaling is mediated via TLR4.
Formal Description
Interaction-ID: 6889

drug/chemical compound

Lipopolysaccharide

increases_activity of

process

toll-like receptor 4 signaling pathway

Comment DJ-1 selectively influences the TLR4 but not the TLR3 pathway.
Formal Description
Interaction-ID: 6890

gene/protein

PARK7

affects_activity of

process

toll-like receptor 4 signaling pathway

Drugbank entries Show/Hide entries for PARK7
Comment DJ-1 selectively influences the TLR4 but not the TLR3 pathway.
Formal Description
Interaction-ID: 6891

gene/protein

PARK7

NOT affects_activity of

process

toll-like receptor 3 signaling pathway

Drugbank entries Show/Hide entries for PARK7
Comment Dj-1-/- astrocytes produced 10 times more NO in response to LPS compared with wild-type controls and reverted to wild-type levels after transduction of DJ-1.
Formal Description
Interaction-ID: 6892

drug/chemical compound

Lipopolysaccharide

increases_quantity of

drug/chemical compound

NO

Comment Loss of DJ-1 leads to excessive iNOS-mediated NO production in primary astrocyte cultures.
Formal Description
Interaction-ID: 6893

gene/protein

NOS2

increases_quantity of

drug/chemical compound

NO

Drugbank entries Show/Hide entries for NOS2
Comment Loss of DJ-1 leads to excessive iNOS-mediated NO production in primary astrocyte cultures.
Formal Description
Interaction-ID: 6894

gene/protein

PARK7

decreases_quantity of

drug/chemical compound

NO

Drugbank entries Show/Hide entries for PARK7
Comment LPS signaling is mediated via TLR4.
Formal Description
Interaction-ID: 6895

gene/protein

TLR4

affects_activity of

process

toll-like receptor 4 signaling pathway

Drugbank entries Show/Hide entries for TLR4
Comment LPS induced NOS2 mRNA and protein expression in a dose-dependent manner. NOS2 expression became significantly higher in DJ-1-/- astrocytes compared with wild-type.
Formal Description
Interaction-ID: 6896

drug/chemical compound

Lipopolysaccharide

increases_expression of

gene/protein

NOS2

Drugbank entries Show/Hide entries for NOS2
Comment LPS induced NOS2 mRNA and protein expression in a dose-dependent manner. NOS2 expression became significantly higher in DJ-1-/- astrocytes compared with wild-type.
Formal Description
Interaction-ID: 6897

drug/chemical compound

Lipopolysaccharide

increases_quantity of

gene/protein

NOS2

Drugbank entries Show/Hide entries for NOS2
Comment The expression levels of DJ-1 were not notably altered in wild-type astrocytes in response to LPS.
Formal Description
Interaction-ID: 6898

drug/chemical compound

Lipopolysaccharide

NOT increases_expression of

gene/protein

PARK7

in astrocytes; in response to LPS
Drugbank entries Show/Hide entries for PARK7
Comment The enhanced NO formation in stimulated Dj-1-knockout astrocytes is due to a specific hyperinduction of the iNOS isoform.
Formal Description
Interaction-ID: 6918

gene/protein

PARK7

affects_activity of

gene/protein

NOS2

via p38MAPK pathway
Drugbank entries Show/Hide entries for PARK7 or NOS2
Comment LPS activated the NF-kappaB pathway in primary astrocyte cultures. However, the percentage of cells with nuclear NF-kappaB was not significant different between Dj-1+/+ and Dj-1-/- astrocytes.
Formal Description
Interaction-ID: 6919

drug/chemical compound

Lipopolysaccharide

increases_activity of

process

I-kappaB kinase/NF-kappaB signaling

in astrocytes
Comment LPS did not stimulate p42/p44 MAPK phosphorylation in primary astrocyte cultures.
Formal Description
Interaction-ID: 6920

drug/chemical compound

Lipopolysaccharide

NOT increases_phosphorylation of

gene/protein

MAPK1

in astrocytes
Drugbank entries Show/Hide entries for MAPK1
Comment LPS did not stimulate p42/p44 MAPK phosphorylation in primary astrocyte cultures.
Formal Description
Interaction-ID: 6921

drug/chemical compound

Lipopolysaccharide

NOT increases_phosphorylation of

gene/protein

MAPK3

in astrocytes
Drugbank entries Show/Hide entries for MAPK3
Comment LPS stimulated transient phosphorylation of the stress-activated protein kinases JNK and p38MAPK. Phosphorylation was significantly stronger in Dj-1-/- astrocyte cultures. Thus, the p38MAPK pathway may be specifically involved in the DJ-1-regulated astrocyte inflammatory responses.
Formal Description
Interaction-ID: 6922

drug/chemical compound

Lipopolysaccharide

increases_phosphorylation of

gene/protein

MAPK8

Drugbank entries Show/Hide entries for MAPK8
Comment LPS stimulated transient phosphorylation of the stress-activated protein kinases JNK and p38MAPK. Phosphorylation was significantly stronger in Dj-1-/- astrocyte cultures. Thus, the p38MAPK pathway may be specifically involved in the DJ-1-regulated astrocyte inflammatory responses.
Formal Description
Interaction-ID: 6927

drug/chemical compound

Lipopolysaccharide

increases_phosphorylation of

gene/protein

p38 MAPK

phosphorylation was significantly stronger in Dj-1-/- astrocyte cultures
Comment LPS stimulated transient phosphorylation of the stress-activated protein kinases JNK and p38MAPK. Phosphorylation was significantly stronger in Dj-1-/- astrocyte cultures. Thus, the p38MAPK pathway may be specifically involved in the DJ-1-regulated astrocyte inflammatory responses.
Formal Description
Interaction-ID: 6930

gene/protein

PARK7

affects_activity of

process

inflammatory response

in astrocytes; via p38MAPK pathway
Drugbank entries Show/Hide entries for PARK7
Comment A second LPS-inducible enzyme generating proinflammatory mediators is COX-2, which produces prostaglandin E2 and is believed to contribute to neuroinflammatory processes in PD, like iNOS.
Formal Description
Interaction-ID: 6934

drug/chemical compound

Lipopolysaccharide

increases_expression of

gene/protein

PTGS2

Drugbank entries Show/Hide entries for PTGS2
Comment A second LPS-inducible enzyme generating proinflammatory mediators is COX-2, which produces prostaglandin E2 and is believed to contribute to neuroinflammatory processes in PD, like iNOS.
Formal Description
Interaction-ID: 6935

gene/protein

PTGS2

increases_quantity of

drug/chemical compound

Prostaglandin

Drugbank entries Show/Hide entries for PTGS2
Comment A second LPS-inducible enzyme generating proinflammatory mediators is COX-2, which produces prostaglandin E2 and is believed to contribute to neuroinflammatory processes in PD, like iNOS.
Formal Description
Interaction-ID: 6936

gene/protein

PTGS2

affects_activity of

process

inflammatory response

via Prostaglandin production
Drugbank entries Show/Hide entries for PTGS2
Comment A second LPS-inducible enzyme generating proinflammatory mediators is COX-2, which produces prostaglandin E2 and is believed to contribute to neuroinflammatory processes in PD, like iNOS.
Formal Description
Interaction-ID: 6937

process

inflammatory response

increases_activity of

disease

Parkinson disease

Comment Ngf was very potently induced by LPS treatment in neonatal astrocyte cultures, independently of DJ1.
Formal Description
Interaction-ID: 6938

drug/chemical compound

Lipopolysaccharide

increases_expression of

gene/protein

NGF

Drugbank entries Show/Hide entries for NGF
Comment Il-6 and COX-2 expression was induced after LPS stimulation to significantly higher levels in Dj-1-/- astrocytes compared with wild-type controls.
Formal Description
Interaction-ID: 6939

drug/chemical compound

Lipopolysaccharide

increases_expression of

gene/protein

IL6

Drugbank entries Show/Hide entries for IL6
Comment Il-6 and COX-2 expression was induced after LPS stimulation to significantly higher levels in Dj-1-/- astrocytes compared with wild-type controls.
Formal Description
Interaction-ID: 6940

gene/protein

PARK7

affects_expression of

gene/protein

IL6

induced by LPS
Drugbank entries Show/Hide entries for PARK7 or IL6
Comment Il-6 and COX-2 expression was induced after LPS stimulation to significantly higher levels in Dj-1-/- astrocytes compared with wild-type controls.
Formal Description
Interaction-ID: 6941

gene/protein

PARK7

affects_expression of

gene/protein

PTGS2

induced by LPS
Drugbank entries Show/Hide entries for PARK7 or PTGS2
Comment LPS stimulated transient phosphorylation of the stress-activated protein kinases JNK and p38MAPK. Phosphorylation was significantly stronger in Dj-1-/- astrocyte cultures. Thus, the p38MAPK pathway may be specifically involved in the DJ-1-regulated astrocyte inflammatory responses.
Formal Description
Interaction-ID: 7484

gene/protein

PARK7

increases_activity of

process

astrocyte activation

via p38MAPK pathway
Drugbank entries Show/Hide entries for PARK7
Comment LPS stimulated transient phosphorylation of the stress-activated protein kinases JNK and p38MAPK. Phosphorylation was significantly stronger in Dj-1-/- astrocyte cultures. Thus, the p38MAPK pathway may be specifically involved in the DJ-1-regulated astrocyte inflammatory responses.
Formal Description
Interaction-ID: 8543

process

astrocyte activation

increases_activity of

process

inflammatory response

Comment LPS stimulated transient phosphorylation of the stress-activated protein kinases JNK and p38MAPK. Phosphorylation was significantly stronger in Dj-1-/- astrocyte cultures. Thus, the p38MAPK pathway may be specifically involved in the DJ-1-regulated astrocyte inflammatory responses.
Formal Description
Interaction-ID: 11691

gene/protein

PARK7

affects_activity of

process

stress-activated MAPK cascade

in astrocytes
Drugbank entries Show/Hide entries for PARK7
Comment LPS signaling is mediated via TLR4.
Formal Description
Interaction-ID: 11729

gene/protein

TLR4

affects_activity of

process

lipopolysaccharide-mediated signaling pathway

Drugbank entries Show/Hide entries for TLR4