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)	PDE5 is also known as PDE5A or 'cGMP-specific 3',5'-cyclic phosphodiesterase'
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		Arrow	EBI-3862570 (IntAct)
TFAM	OXPHOS capacity	Arrow	WP3331 (WikiPathways)
ZNF746	PPARGC1A	mim-inhibition	EBI-3989372 (IntAct)
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]. Type your comment here
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].