General Information:

Id: 655
Diseases: Amyotrophic lateral sclerosis
Mus musculus
BTO:0004488 NSC-34 cell
article
Reference: Kupershmidt L et al.(2009) Neuroprotective and neuritogenic activities of novel multimodal iron-chelating drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis FASEB J. 23: 3766-3779 [PMID: 19638399]

Interaction Information:

Comment Treatment of NSC-34 cells with the iron-chelating drugs, M30 and HLA20 significantly reduced cell mortality induced by H2O2 and SIN-1 (3-Morpholinosydnonimine, a potent peroxynitrite ion generator). In these concentrations, M30 and HLA20 alone, in the absence of the neurotoxins, had no effect on cell viability, relative to control.
Formal Description
Interaction-ID: 3471

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

decreases_activity of

induced by H2O2 or SIN-1
Comment Treatment of NSC-34 cells with the iron-chelating drugs, M30 and HLA20 significantly reduced cell mortality induced by H2O2 and SIN-1 (3-Morpholinosydnonimine, a potent peroxynitrite ion generator). In these concentrations, M30 and HLA20 alone, in the absence of the neurotoxins, had no effect on cell viability, relative to control.
Formal Description
Interaction-ID: 3486

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

decreases_activity of

induced by H2O2 or SIN-1
Comment M30 and HLA20 induced a dose-dependent increase in TfR levels in, confirming the iron chelation effect of these drugs in NSC-34 cells.
Formal Description
Interaction-ID: 3487

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_quantity of

gene/protein

TFRC

Comment M30 and HLA20 induced a dose-dependent increase in TfR levels in, confirming the iron chelation effect of these drugs in NSC-34 cells.
Formal Description
Interaction-ID: 3488

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_quantity of

gene/protein

TFRC

Comment The levels of both mRNA and protein expression of HIF-1 alpha were increased in M30- and HLA20-treated NSC-34 cells, indicating that the drugs not only stabilized HIF-1 alpha protein but influenced its regulation on the transcriptional level.
Formal Description
Interaction-ID: 3489

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

HIF1A

Drugbank entries Show/Hide entries for HIF1A
Comment The levels of both mRNA and protein expression of HIF-1 alpha were increased in M30- and HLA20-treated NSC-34 cells, indicating that the drugs not only stabilized HIF-1 alpha protein but influenced its regulation on the transcriptional level.
Formal Description
Interaction-ID: 3490

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_quantity of

gene/protein

HIF1A

Drugbank entries Show/Hide entries for HIF1A
Comment The levels of both mRNA and protein expression of HIF-1 alpha were increased in M30- and HLA20-treated NSC-34 cells, indicating that the drugs not only stabilized HIF-1 alpha protein but influenced its regulation on the transcriptional level.
Formal Description
Interaction-ID: 3491

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

HIF1A

Drugbank entries Show/Hide entries for HIF1A
Comment The levels of both mRNA and protein expression of HIF-1 alpha were increased in M30- and HLA20-treated NSC-34 cells, indicating that the drugs not only stabilized HIF-1 alpha protein but influenced its regulation on the transcriptional level.
Formal Description
Interaction-ID: 3492

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_quantity of

gene/protein

HIF1A

Drugbank entries Show/Hide entries for HIF1A
Comment Exposure of NSC-34 cells to M30 or HLA20 significantly increased mRNA levels of VEGF and enolase 1, two known HIF-1-regulated genes.
Formal Description
Interaction-ID: 3493

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

VEGFA

Drugbank entries Show/Hide entries for VEGFA
Comment Exposure of NSC-34 cells to M30 or HLA20 significantly increased mRNA levels of VEGF and enolase 1, two known HIF-1-regulated genes.
Formal Description
Interaction-ID: 3494

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

ENO1

Comment Exposure of NSC-34 cells to M30 or HLA20 significantly increased mRNA levels of VEGF and enolase 1, two known HIF-1-regulated genes.
Formal Description
Interaction-ID: 3495

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

VEGFA

Drugbank entries Show/Hide entries for VEGFA
Comment Exposure of NSC-34 cells to M30 or HLA20 significantly increased mRNA levels of VEGF and enolase 1, two known HIF-1-regulated genes.
Formal Description
Interaction-ID: 3496

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

ENO1

Comment M30 and HLA20 markedly increased the amount of phospho-AKT at 30 min of drug exposure.
Formal Description
Interaction-ID: 3497

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment M30 and HLA20 markedly increased the amount of phospho-AKT at 30 min of drug exposure.
Formal Description
Interaction-ID: 3498

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

AKT1

at Ser-473
Drugbank entries Show/Hide entries for AKT1
Comment M30 and HLA20 markedly increased the amount of phospho-AKT at 30 min of drug exposure.
Formal Description
Interaction-ID: 3499

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment M30 and HLA20 markedly increased the amount of phospho-AKT at 30 min of drug exposure.
Formal Description
Interaction-ID: 3500

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

AKT1

at Ser-473
Drugbank entries Show/Hide entries for AKT1
Comment M30 and HLA20 significantly increased phosphorylation of GSK-3-beta at Ser-9 in NSC-34 cells, suggesting that both drugs induced activation of AKT followed by phosphorylation (inactivation) of GSK-3-beta.
Formal Description
Interaction-ID: 3501

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

GSK3B

at Ser-9
Drugbank entries Show/Hide entries for GSK3B
Comment M30 and HLA20 significantly increased phosphorylation of GSK-3-beta at Ser-9 in NSC-34 cells, suggesting that both drugs induced activation of AKT followed by phosphorylation (inactivation) of GSK-3-beta.
Formal Description
Interaction-ID: 3529

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

decreases_activity of

gene/protein

GSK3B

by phosphorylation of GSK3B at Ser-9
Drugbank entries Show/Hide entries for GSK3B
Comment M30 and HLA20 significantly increased phosphorylation of GSK-3-beta at Ser-9 in NSC-34 cells, suggesting that both drugs induced activation of AKT followed by phosphorylation (inactivation) of GSK-3-beta.
Formal Description
Interaction-ID: 3530

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

GSK3B

at Ser-9
Drugbank entries Show/Hide entries for GSK3B
Comment M30 and HLA20 significantly increased phosphorylation of GSK-3-beta at Ser-9 in NSC-34 cells, suggesting that both drugs induced activation of AKT followed by phosphorylation (inactivation) of GSK-3-beta.
Formal Description
Interaction-ID: 3531

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

decreases_activity of

gene/protein

GSK3B

by phosphorylation of GSK3B at Ser-9
Drugbank entries Show/Hide entries for GSK3B
Comment M30 and HLA20 induced NSC-34 neuritogenesis, accompanied by a marked increase in the expression of brain-derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43).
Formal Description
Interaction-ID: 3534

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

BDNF

Comment M30 and HLA20 induced NSC-34 neuritogenesis, accompanied by a marked increase in the expression of brain-derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43).
Formal Description
Interaction-ID: 3535

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

GAP43

Comment M30 and HLA20 induced NSC-34 neuritogenesis, accompanied by a marked increase in the expression of brain-derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43).
Formal Description
Interaction-ID: 3536

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

BDNF

Comment M30 and HLA20 induced NSC-34 neuritogenesis, accompanied by a marked increase in the expression of brain-derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43).
Formal Description
Interaction-ID: 3537

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_expression of

gene/protein

GAP43

Comment M30 and HLA20 markedly reduced the levels of cyclin D1.
Formal Description
Interaction-ID: 3538

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

decreases_quantity of

gene/protein

CCND1

Drugbank entries Show/Hide entries for CCND1
Comment M30 and HLA20 markedly reduced the levels of cyclin D1.
Formal Description
Interaction-ID: 3539

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

decreases_quantity of

gene/protein

CCND1

Drugbank entries Show/Hide entries for CCND1
Comment M30 and HLA20 caused a rapid phosphorylation of PKC and ERK1/2 in NSC-34 cells at 10 min, reaching a maximum at 20 min.
Formal Description
Interaction-ID: 3540

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

MAPK3

Drugbank entries Show/Hide entries for MAPK3
Comment M30 and HLA20 caused a rapid phosphorylation of PKC and ERK1/2 in NSC-34 cells at 10 min, reaching a maximum at 20 min.
Formal Description
Interaction-ID: 3541

drug/chemical compound

(5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

MAPK1

Drugbank entries Show/Hide entries for MAPK1
Comment M30 and HLA20 caused a rapid phosphorylation of PKC and ERK1/2 in NSC-34 cells at 10 min, reaching a maximum at 20 min.
Formal Description
Interaction-ID: 3542

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

MAPK3

Drugbank entries Show/Hide entries for MAPK3
Comment M30 and HLA20 caused a rapid phosphorylation of PKC and ERK1/2 in NSC-34 cells at 10 min, reaching a maximum at 20 min.
Formal Description
Interaction-ID: 3543

drug/chemical compound

(5-[4-propargylpiperazin-1-ylmethyl]-8-hydroxyquinoline)

increases_phosphorylation of

gene/protein

MAPK1

Drugbank entries Show/Hide entries for MAPK1