Sildenafil treatment (Homo sapiens)

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History

External references

DataNodes

Name	Type	Database reference	Comment
AKT1	GeneProduct	ENSG00000142208 (Ensembl)
AKT2	GeneProduct	ENSG00000105221 (Ensembl)
AKT3	GeneProduct	ENSG00000117020 (Ensembl)
AMP	Metabolite	CHEBI:16027 (ChEBI)
Calcium homeostasis	Pathway	WP4088 (WikiPathways)
GAPDH inhibitors	Metabolite	CHEBI:70817 (ChEBI)
GAPDH	GeneProduct	ENSG00000111640 (Ensembl)
GMP	Metabolite	CHEBI:17345 (ChEBI)
GSK3B	GeneProduct	ENSG00000082701 (Ensembl)
GTP	Metabolite	CHEBI:37565 (ChEBI)
GUCY1A1	GeneProduct	ENSG00000164116 (Ensembl)	Also known as GUCY1A3 [uniprot:Q02108].
GUCY1A2	GeneProduct	ENSG00000152402 (Ensembl)
GUCY1B1	GeneProduct	ENSG00000061918 (Ensembl)	Also known as GUCY1B3 [uniprot:Q02153].
GUCY1B2	GeneProduct	ENSG00000123201 (Ensembl)
MAPK pathway	Pathway	WP382 (WikiPathways)
Mitochondrial biogenesis	Pathway	WP3331 (WikiPathways)
Mitochondrial membrane potential	Pathway	R-HSA-8949215 (Reactome)
NO-signaling	Pathway	WP1850 (WikiPathways)
NOS1	GeneProduct	ENSG00000089250 (Ensembl)
NOS2	GeneProduct	ENSG00000007171 (Ensembl)
NOS3	GeneProduct	ENSG00000164867 (Ensembl)	NOS3 is implicated in vascular smooth muscle relaxation through cGMP [PMID:1378832,PMID:20590592].
NRF1	GeneProduct	ENSG00000106459 (Ensembl)
Neurogenesis	Pathway	R-HSA-9675108 (Reactome)
Nitric oxide	Metabolite	CHEBI:16480 (ChEBI)
OXPHOS capacity	Pathway	WP111 (WikiPathways)
PDE4 inhibitors	Metabolite	CHEBI:68844 (ChEBI)
PDE4A	GeneProduct	ENSG00000065989 (Ensembl)
PDE4B	GeneProduct	ENSG00000184588 (Ensembl)
PDE4C	GeneProduct	ENSG00000105650 (Ensembl)
PDE4D	GeneProduct	ENSG00000113448 (Ensembl)
PDE5	GeneProduct	ENSG00000138735 (Ensembl)	Inhibition of cGMP degradation by PDE5 increases cGMP availability [PMID:9714779].
PI3K Cascade	Pathway	WP4448 (WikiPathways)	AKT is activated through phosphorylation upon recruitement to the cell membrane
PPARGC1A	GeneProduct	ENSG00000109819 (Ensembl)	Alternative name is PGC1A [uniprot:Q9UBK2]
PRKG1	GeneProduct	ENSG00000185532 (Ensembl)
PRKN	GeneProduct	ENSG00000185345 (Ensembl)
Smooth muscle relaxation	Pathway	R-HSA-418457 (Reactome)
Synaptic transmission	Pathway	R-HSA-112310.5 (Reactome)
TFAM	GeneProduct	ENSG00000108064 (Ensembl)
ZNF746	GeneProduct	ENSG00000181220 (Ensembl)
cGMP	Metabolite	CHEBI:16356 (ChEBI)
sildenafil	Metabolite	CHEBI:9139 (ChEBI)
tideglusib	Metabolite	CHEBI:147398 (ChEBI)

Annotated Interactions

Source	Target	Type	Database reference	Comment
AKT	Mitochondrial membrane potential	Arrow	R-HSA-04151 (Reactome)	The family of AKT proteins stabalize mitochondrial membrane potential through TCL1A [uniprot:P56279] and TCL1B [unirprot:O95988]. [PMID:10983986,PMID:11839817]
AKT	Neurogenesis	Arrow	R-HSA-157118 (Reactome)	Negative regulation of neuronal death [GO:1901215] Regulation of neuron projection development [GO:0010975]
AKT	PPARGC1A	Arrow	R-HSA-04151 (Reactome)
GAPDH inhibitors	GAPDH	mim-inhibition	CHEBI:70817 (ChEBI)
GAPDH	AKT	mim-stimulation	EBI-7982916 (IntAct)	GAPDH can bind AKT to limit dephosphorylation, prolonging AKT activity and therefor increase mitochondrial membrane potential stabilization [PMID:23645209].
GTP	cGMP	mim-conversion	4.6.1.2 (BRENDA)
NOS	GAPDH	Arrow	EBI-10091848 (IntAct)
NOS	Nitric oxide	mim-conversion	1.14.13.39 (BRENDA)	The family of nitric oxide synthases produce nitric oxide (NO) from L-argine, oxigen and NAPDH [PMID:1722402,PMID:1662386].
NRF1	TFAM	mim-transcription-translation	WP3331 (WikiPathways)
Nitric oxide	sGC	mim-binding	R-HSA-392154 (Reactome)	Soluble guanylyl cyclases (sGC) are activated by nitric oxide (NO) [PMID:9742212].
PDE4 inhibitors	PDE4	TBar	CHEBI:68844 (ChEBI)
PDE4	AMP	mim-catalysis	3.1.4.53 (BRENDA)	The family of PDE4s (cAMP-specific 3',5'-cyclic phosphodiesterases) hydrolyse cAMP into AMP.
PDE5		mim-catalysis	3.1.4.35 (BRENDA)	Inhibition of cGMP degradation by PDE5 increases cGMP availability [PMID:9714779].
PPARGC1A	NRF1	mim-transcription-translation	WP3331 (WikiPathways)	Transcriptional coactivator
PRKG1	AKT	Arrow	R-HSA-1257604 (Reactome)
PRKN	ZNF746	Arrow	EBI-3862570 (IntAct)
TFAM	OXPHOS capacity	Arrow	WP3331 (WikiPathways)
ZNF746	PPARGC1A	mim-inhibition	EBI-3989372 (IntAct)	Repressed transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in regulation of neuron death [PMID:21376232]
cGMP		Arrow	2.7.11.12 (BRENDA)
cGMP	Smooth muscle relaxation	Arrow	R-HSA-418457 (Reactome)	An increase in cGMP leads to smooth muscle relaxation and therefore relieve the symptoms of erectile disfunction [PMID:2545495,PMID:8813924].
cGMP		mim-conversion	3.1.4.35 (BRENDA)	cGMP is converted into GMP through hydrolysis by PDE5 [PMID:7870041].
sGC	PRKG1	Arrow	R-HSA-392154 (Reactome)
sGC		mim-stimulation	4.6.1.2 (BRENDA)	sGCs catalyze the conversion of GTP into GMP.
sildenafil	PDE5	TBar	DB00203 (DrugBank)
tideglusib	GSK3B	TBar	DB12129 (DrugBank)	Glycogen synthase kinase 3beta (GSK3beta) tideglusib (NP031112) has anti-inflammatory and neuroprotective properties [PMID:17522320].