CIDeRGeneral Information:
| Id: | 404 (click here to show other Interactions for entry) |
| Diseases: |
Amyotrophic lateral sclerosis
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| 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. |
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Formal Description Interaction-ID: 1724 |
gene/protein mutant increases_expression of gene/protein |
| 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. |
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Formal Description Interaction-ID: 1727 |
gene/protein mutant increases_expression of gene/protein |
| 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. |
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Formal Description Interaction-ID: 1728 |
gene/protein mutant decreases_activity of process |
| 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. |
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Formal Description Interaction-ID: 1732 |
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| 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). |
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Formal Description Interaction-ID: 1733 |
gene/protein mutant NOT affects_expression of gene/protein |
| 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. |
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Formal Description Interaction-ID: 1735 |
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| 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. |
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Formal Description Interaction-ID: 1767 |
gene/protein mutant increases_activity of process |
| 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. |
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Formal Description Interaction-ID: 1768 |
gene/protein mutant increases_activity of phenotype |
| Comment | The expression of P2X4, P2Y2, and P2Y12 mRNAs did not change significantly in hSOD1-G93A immortalized or primary microglia. |
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Formal Description Interaction-ID: 13503 |
gene/protein mutant NOT increases_expression of gene/protein |
| Comment | The expression of P2X4, P2Y2, and P2Y12 mRNAs did not change significantly in hSOD1-G93A immortalized or primary microglia. |
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Formal Description Interaction-ID: 13506 |
gene/protein mutant NOT increases_expression of gene/protein |
| 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. |
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Formal Description Interaction-ID: 13508 |
gene/protein mutant NOT increases_expression of gene/protein |
| 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. |
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Formal Description Interaction-ID: 13509 |
gene/protein mutant increases_quantity of gene/protein |
| Comment | There was an increase of receptor proteins P2X4 and P2X7 in hSOD1-G93A immortalized or primary microglia. |
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Formal Description Interaction-ID: 13510 |
gene/protein mutant increases_quantity of gene/protein |
| 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. |
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Formal Description Interaction-ID: 13520 |
gene/protein mutant affects_activity of |