)| PMID |
18422522 ( ) |
|---|---|
| Title | Endothelial nitric oxide synthase overexpression by neuronal cells in neurodegeneration: a link between inflammation and neuroprotection. |
| Abstract | The roles of neuronal and inducible nitric oxide synthases in neurones have been extensively investigated; by contrast, the biological significance of endothelial nitric oxide synthase (eNOS) overexpression that occurs in several pathological conditions has not yet been studied. We have started addressing this issue in a cell model of neurodegeneration, i.e. human SKNBE neuroblastoma cells transfected with a mutant form of alsin, a protein causing an early-onset type of amyotrophic lateral sclerosis, ALS2. We found that eNOS, which is endogenously expressed by these cells, was activated by tumour necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine that plays important roles in ALS2 and several neurodegenerative diseases. The TNF-alpha-dependent eNOS activation occurred through generation, by sphingosine-kinase-1, of sphingosine-1-phosphate, stimulation of its membrane receptors and activation of Akt, as determined using small interference RNA and dominant negative constructs specific for the enzymes and receptors. eNOS activation by TNF-alpha conferred cytoprotection from excitotoxicity and neurotoxic cues such as reactive oxygen species, endoplasmic reticulum stress, DNA damage, and mutated alsin itself. Our results suggest that overexpression of eNOS by neurones is a broad-range protective mechanism activated during damage and establish a link of pathophysiological relevance between this enzyme and inflammation accompanying neurodegenerative diseases. These findings also question the concept that high NO output in the presence of oxidative stress leads always to peroxynitrite formation contributing to neurodegeneration. Italy. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 7 | endothelial nitric oxide synthase | eNOS | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 6 | TNF-alpha-dependent | tnf alpha | |
| 443 | ALS2 | amyotrophic lateral sclerosis 2 (juvenile) | 2 | ALS2 | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 1 | Akt | |
| 11240 | SPHK1 | sphingosine kinase 1 | 1 | sphingosine kinase 1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | contrast the biological significance of endothelial nitric oxide synthase (eNOS) eNOS overexpression that occurs in several pathological conditions has not yet |
| 443 | ALS2 | amyotrophic lateral sclerosis 2 (juvenile) | ALS2 | 1.5 | a protein causing an early-onset type of amyotrophic lateral sclerosis ALS2 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | We found that eNOS which is endogenously expressed by these cells was activated by |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.8 | by these cells was activated by tumour necrosis factor-alpha (TNF-alpha), TNF-alpha a proinflammatory cytokine that plays important roles in ALS2 and |
| 443 | ALS2 | amyotrophic lateral sclerosis 2 (juvenile) | ALS2 | 1.5 | (TNF-alpha), TNF-alpha a proinflammatory cytokine that plays important roles in ALS2 and several neurodegenerative diseases |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha-dependent | 1.8 | The TNF-alpha-dependent eNOS activation occurred through generation by sphingosine-kinase-1 of sphingosine-1-phosphate stimulation |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | The TNF-alpha-dependent eNOS activation occurred through generation by sphingosine-kinase-1 of sphingosine-1-phosphate stimulation of |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | and dominant negative constructs specific for the enzymes and receptors eNOS activation by TNF-alpha conferred cytoprotection from excitotoxicity and neurotoxic cues |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.8 | constructs specific for the enzymes and receptors eNOS activation by TNF-alpha conferred cytoprotection from excitotoxicity and neurotoxic cues such as reactive |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | of sphingosine-1-phosphate stimulation of its membrane receptors and activation of Akt as determined using small interference RNA and dominant negative constructs |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | Our results suggest that overexpression of eNOS by neurones is a broad-range protective mechanism activated during damage |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | endothelial nitric oxide synthase overexpression by neuronal cells in neurodegeneration: a link between inflammation and neuroprotection. |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | the roles of neuronal and inducible nitric oxide synthases in neurones have been extensively investigated; by contrast the biological significance of endothelial nitric oxide synthase enos overexpression that occurs in several pathological conditions has not yet been studied. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we found that enos which is endogenously expressed by these cells was activated by tumour necrosis factor alpha tnf alpha a proinflammatory cytokine that plays important roles in als2 and several neurodegenerative diseases. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the tnf alpha dependent enos activation occurred through generation by sphingosine kinase 1 of sphingosine 1 phosphate stimulation of its membrane receptors and activation of akt as determined using small interfer |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | hate stimulation of its membrane receptors and activation of akt as determined using small interference rna and dominant negative constructs specific for the enzymes and receptors. enos activation by tnf alpha conferred cytoprotection from excitotoxicity and neurotoxic cues such as reactive oxygen species endoplasmic reticulum stress dna damage and mutated alsin itself. |
| 11240 | SPHK1 | sphingosine kinase 1 | sphingosine kinase 1 | 1.0 | the tnf alpha dependent enos activation occurred through generation by sphingosine kinase 1 of sphingosine 1 phosphate stimulation of its membrane receptors and activation of akt as determined using small interference rna and dominant negative constructs specific for the enzymes and recepto |