General Information:

Id: 1,074
Diseases: Amyotrophic lateral sclerosis
Mammalia
BTO:0001976 Neuro-2a cell
article
Reference: Zhong Z et al.(2009) Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells J. Clin. Invest. 119: 3437-3449 [PMID: 19841542]

Interaction Information:

Comment N2a neuroblastoma cells expressing an ALS-linked mutant SOD1G85R (N2a-SOD1G85R cells) confirmed that APC (WT-APC and mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity)) can act directly on neuronal cells to selectively downregulate SOD1G85R and endogenous mouse SOD1 mRNA.
Formal Description
Interaction-ID: 6777

gene/protein mutant

PROC-mut

decreases_expression of

gene/protein

SOD1

Drugbank entries Show/Hide entries for SOD1
Comment N2a neuroblastoma cells expressing an ALS-linked mutant SOD1G85R (N2a-SOD1G85R cells) confirmed that APC (WT-APC and mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity)) can act directly on neuronal cells to selectively downregulate SOD1G85R and endogenous mouse SOD1 mRNA.
Formal Description
Interaction-ID: 6778

gene/protein mutant

PROC-mut

decreases_expression of

gene/protein mutant

SOD1-p.G85R

Comment N2a neuroblastoma cells expressing an ALS-linked mutant SOD1G85R (N2a-SOD1G85R cells) confirmed that mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity)) can act directly on neuronal cells to selectively downregulate SOD1G85R and endogenous mouse SOD1 protein levels.
Formal Description
Interaction-ID: 6779

gene/protein mutant

PROC-mut

decreases_quantity of

gene/protein

SOD1

Drugbank entries Show/Hide entries for SOD1
Comment N2a neuroblastoma cells expressing an ALS-linked mutant SOD1G85R (N2a-SOD1G85R cells) confirmed that mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity)) can act directly on neuronal cells to selectively downregulate SOD1G85R and endogenous mouse SOD1 protein levels.
Formal Description
Interaction-ID: 6780

gene/protein mutant

PROC-mut

decreases_quantity of

gene/protein mutant

SOD1-p.G85R

Comment The 5A-APC-PAR1/PAR3 pathway blocked nuclear translocation of transcription factor Sp1 in N2a-SOD1G85R-expressing cells. APC's activation of PAR1 and PAR3 can suppress activity of transcription factors. Blockage of PAR1 and PAR3 activation, but not that of PAR2 and PAR4, abolished mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) -mediated downregulation of SOD1.
Formal Description
Interaction-ID: 6781

gene/protein mutant

PROC-mut

increases_activity of

gene/protein

F2R

Drugbank entries Show/Hide entries for F2R
Comment The 5A-APC-PAR1/PAR3 pathway blocked nuclear translocation of transcription factor Sp1 in N2a-SOD1G85R-expressing cells. APC's activation of PAR1 and PAR3 can suppress activity of transcription factors. Blockage of PAR1 and PAR3 activation, but not that of PAR2 and PAR4, abolished mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) -mediated downregulation of SOD1.
Formal Description
Interaction-ID: 6787

gene/protein mutant

PROC-mut

increases_activity of

gene/protein

F2RL2

Comment The 5A-APC-PAR1/PAR3 pathway blocked nuclear translocation of transcription factor Sp1 in N2a-SOD1G85R-expressing cells. APC's activation of PAR1 and PAR3 can suppress activity of transcription factors. Blockage of PAR1 and PAR3 activation, but not that of PAR2 and PAR4, abolished mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) -mediated downregulation of SOD1.
Formal Description
Interaction-ID: 6788

gene/protein mutant

PROC-mut

NOT affects_activity of

gene/protein

F2RL1

Comment The 5A-APC-PAR1/PAR3 pathway blocked nuclear translocation of transcription factor Sp1 in N2a-SOD1G85R-expressing cells. APC's activation of PAR1 and PAR3 can suppress activity of transcription factors. Blockage of PAR1 and PAR3 activation, but not that of PAR2 and PAR4, abolished mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) -mediated downregulation of SOD1.
Formal Description
Interaction-ID: 6789

gene/protein mutant

PROC-mut

NOT affects_activity of

gene/protein

F2RL3

Comment Neuroprotection by APC reduces hemoglobin and ROS toxicity. Addition of mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) at concentrations comparable to therapeutically effective levels in SOD1G93A mice abolished hemoglobin (Hb)-induced toxicity and lowered detectable levels of ROS. S360A-APC was ineffective in improving cell survival or preventing ROS generation.
Formal Description
Interaction-ID: 6790

gene/protein mutant

PROC-mut

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Neuroprotection by APC reduces hemoglobin and ROS toxicity. Addition of mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) at concentrations comparable to therapeutically effective levels in SOD1G93A mice abolished hemoglobin (Hb)-induced toxicity and lowered detectable levels of ROS. S360A-APC was ineffective in improving cell survival or preventing ROS generation.
Formal Description
Interaction-ID: 6792

gene/protein mutant

PROC-mut

decreases_activity of

process

neuron death

Comment Neuroprotection by APC reduces hemoglobin and ROS toxicity. Addition of mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) at concentrations comparable to therapeutically effective levels in SOD1G93A mice abolished hemoglobin (Hb)-induced toxicity and lowered detectable levels of ROS. S360A-APC was ineffective in improving cell survival or preventing ROS generation.
Formal Description
Interaction-ID: 6793

gene/protein mutant

PROC-p.S360A

NOT decreases_activity of

process

neuron death

Comment Neuroprotection by APC reduces hemoglobin and ROS toxicity. Addition of mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) at concentrations comparable to therapeutically effective levels in SOD1G93A mice abolished hemoglobin (Hb)-induced toxicity and lowered detectable levels of ROS. S360A-APC was ineffective in improving cell survival or preventing ROS generation.
Formal Description
Interaction-ID: 6794

gene/protein mutant

PROC-p.S360A

NOT decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) also protected N2a-SOD1G85R cells from excitotoxic overstimulation of NMDA glutamate receptors.
Formal Description
Interaction-ID: 6795

gene/protein mutant

PROC-mut

decreases_activity of

phenotype

abnormal glutamate-mediated receptor currents

Comment The 5A-APC-PAR1/PAR3 pathway blocked nuclear translocation of transcription factor Sp1 in N2a-SOD1G85R-expressing cells. Treatment with mutant 5A-APC (having 10% of the anticoagulant activity of WT-APC but retaining normal cytoprotective activity) significantly reduced nuclear Sp1 by 60% compared with untreated controls.
Formal Description
Interaction-ID: 6796

gene/protein mutant

PROC-mut

decreases_quantity of

gene/protein

SP1

in nucleus