General Information:

Id: 404
Diseases: Amyotrophic lateral sclerosis
Mus musculus
SOD1G93A transgenic mouse, transfected with human SOD1G93A
BTO:0000078 microglia
article
Reference: D'Ambrosi N et al.(2009) The proinflammatory action of microglial P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis J. Immunol. 183: 4648-4656 [PMID: 19734218]

Interaction Information:

Comment There was an increase for P2X7 and P2Y6 mRNAs in immortalized hSOD1-G93A cells vs nt cells, whereas in primary hSOD1-G93A microglia only P2Y6 mRNA was significantly up-regulated. ATP, BzATP, and UDP are ligands known to activate these P2 receptors.
Formal Description
Interaction-ID: 1724

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

P2RX7

in immortalized microglia
Comment There was an increase for P2X7 and P2Y6 mRNAs in immortalized hSOD1-G93A cells vs nt cells, whereas in primary hSOD1-G93A microglia only P2Y6 mRNA was significantly up-regulated. ATP, BzATP, and UDP are ligands known to activate these P2 receptors.
Formal Description
Interaction-ID: 1727

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

P2RY6

in immortalized microglia
Comment The experiments showed a down-regulation of ATP-hydrolyzing activities in mutant SOD1 microglia. Immortalized nontransgenic microglia degraded extracellular ATP more efficiently than hSOD1-G93A cells.
Formal Description
Interaction-ID: 1728

gene/protein mutant

SOD1-p.G93A

decreases_activity of

in immortalized microglia
Comment Under basal conditions, the expression of TNF-alpha was increased in immortalized hSOD1-G93A microglia, with respect to nontransgenic cells. The addition of extracellular ATP and BzATP (2'-3'-O-(benzoyl-benzoyl) ATP) increased TNF-alpha content in all cases, but with a higher level of induction in immortalized and primary hSOD1-G93A cells.
Formal Description
Interaction-ID: 1732

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

TNF

in immortalized microglia
Drugbank entries Show/Hide entries for TNF
Comment Overexpression of hSOD1-G93A is not sufficient to preactivate microglial cells to produce pro-IL-1-beta even after treatment with either ATP, BzATP (2'-3'-O-(benzoyl-benzoyl) ATP) or UDP (uridine diphosphate).
Formal Description
Interaction-ID: 1733

gene/protein mutant

SOD1-p.G93A

NOT affects_expression of

gene/protein

IL1B

in immortalized microglia
Drugbank entries Show/Hide entries for IL1B
Comment Immortalized hSOD1-G93A transgenic cells exhibit significantly higher basal expression of COX-2. The addition of extracellular ATP and BzATP (2'-3'-O-(benzoyl-benzoyl) ATP) increased COX-2 content in immortalized and primary hSOD1-G93A cells.
Formal Description
Interaction-ID: 1735

gene/protein mutant

SOD1-p.G93A

increases_quantity of

gene/protein

PTGS2

in immortalized microglia
Drugbank entries Show/Hide entries for PTGS2
Comment BzATP was found as the most effective agonist in switching hSOD1-G93A microglia from resting to activated state, in terms of cellular morphology, synthesis of TNF-alpha and COX-2 (but not IL-1-beta) proinflammatory factors, as well as in inducing consequent detrimental effects on neurons.
Formal Description
Interaction-ID: 1767

gene/protein mutant

SOD1-p.G93A

increases_activity of

in SOD1G93A transgenic mice
Comment BzATP was found as the most effective agonist in switching hSOD1-G93A microglia from resting to activated state, in terms of cellular morphology, synthesis of TNF-alpha and COX-2 (but not IL-1-beta) proinflammatory factors, as well as in inducing consequent detrimental effects on neurons.
Formal Description
Interaction-ID: 1768

gene/protein mutant

SOD1-p.G93A

increases_activity of

in SOD1G93A transgenic mice
Comment The expression of P2X4, P2Y2, and P2Y12 mRNAs did not change significantly in hSOD1-G93A immortalized or primary microglia.
Formal Description
Interaction-ID: 13503

gene/protein mutant

SOD1-p.G93A

NOT increases_expression of

gene/protein

P2RX4

in immortalized and primary microglia
Comment The expression of P2X4, P2Y2, and P2Y12 mRNAs did not change significantly in hSOD1-G93A immortalized or primary microglia.
Formal Description
Interaction-ID: 13506

gene/protein mutant

SOD1-p.G93A

NOT increases_expression of

gene/protein

P2RY2

in immortalized and primary microglia
Drugbank entries Show/Hide entries for P2RY2
Comment The expression of P2X4, P2Y2, and P2Y12 mRNAs did not change significantly in hSOD1-G93A immortalized or primary microglia.
Formal Description
Interaction-ID: 13508

gene/protein mutant

SOD1-p.G93A

NOT increases_expression of

gene/protein

P2RY12

in immortalized and primary microglia
Drugbank entries Show/Hide entries for P2RY12
Comment There was an increase of receptor proteins P2X4 and P2X7 in hSOD1-G93A immortalized or primary microglia.
Formal Description
Interaction-ID: 13509

gene/protein mutant

SOD1-p.G93A

increases_quantity of

gene/protein

P2RX4

in immortalized and primary microglia
Comment There was an increase of receptor proteins P2X4 and P2X7 in hSOD1-G93A immortalized or primary microglia.
Formal Description
Interaction-ID: 13510

gene/protein mutant

SOD1-p.G93A

increases_quantity of

gene/protein

P2RX7

in immortalized and primary microglia
Comment The induction of the ALS phenotype through hSOD1-G93A expression has a direct impact on purinergic signaling in microglia. ATP can reach high levels in the extracellular space as a consequence of release from both dying or abnormally functioning cells. It acts as a neuron-to-microglia alarm signal, through cell surface P2 receptors widely distributed throughout the CNS.
Formal Description
Interaction-ID: 13520

gene/protein mutant

SOD1-p.G93A

affects_activity of

in immortalized and primary microglia
Comment The addition of extracellular ATP and BzATP (the most effective agonist) increased TNF-alpha content in all cases, but with a higher level of induction in immortalized and primary hSOD1-G93A cells. In general, BzATP was always more potent than ATP in increasing overall TNF-alpha content, with maximum levels reached in ALS-linked immortalized and primary cells.
Formal Description
Interaction-ID: 13527

drug/chemical compound

ATP

increases_quantity of

gene/protein

TNF

in immortalized and primary microglia
Drugbank entries Show/Hide entries for TNF
Comment The addition of extracellular ATP and BzATP (the most effective agonist) increased COX-2 content in in immortalized and primary hSOD1-G93A cells.
Formal Description
Interaction-ID: 13544

drug/chemical compound

ATP

increases_quantity of

gene/protein

PTGS2

in immortalized and primary microglia
Drugbank entries Show/Hide entries for PTGS2
Comment The addition of extracellular ATP and BzATP (the most effective agonist) increased TNF-alpha content in all cases, but with a higher level of induction in immortalized and primary hSOD1-G93A cells. In general, BzATP was always more potent than ATP in increasing overall TNF-alpha content, with maximum levels reached in ALS-linked immortalized and primary cells.
Formal Description
Interaction-ID: 13546

drug/chemical compound

3'-O-(4-Benzoyl)benzoyl ATP

increases_quantity of

gene/protein

TNF

in immortalized and primary microglia
Drugbank entries Show/Hide entries for TNF
Comment The addition of extracellular ATP and BzATP (the most effective agonist) increased COX-2 content in in immortalized and primary hSOD1-G93A cells.
Formal Description
Interaction-ID: 13547

drug/chemical compound

3'-O-(4-Benzoyl)benzoyl ATP

increases_quantity of

gene/protein

PTGS2

in immortalized and primary microglia
Drugbank entries Show/Hide entries for PTGS2