Sildenafil treatment (WP5294)

Homo sapiens

Sildenafil treatment

Authors

Cenna Doornbos , Egon Willighagen , Denise Slenter , and Eric Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

mitochondrial disease pathway

Disease Ontology

pulmonary hypertension impotence hypertension

Participants

Label Type Compact URI Comment
cGMP Metabolite chebi:16356
Nitric oxide Metabolite chebi:16480
AMP Metabolite chebi:16027
GTP Metabolite chebi:37565
GAPDH inhibitors Metabolite chebi:70817
GMP Metabolite chebi:17345
Tideglusib Metabolite chebi:147398
Sildenafil Metabolite chebi:9139
PDE4inhibitors Metabolite chebi:68844
AKT1 GeneProduct ensembl:ENSG00000142208
TFAM GeneProduct ensembl:ENSG00000108064
PRKG1 GeneProduct ensembl:ENSG00000185532
PRKN GeneProduct ensembl:ENSG00000185345
AKT2 GeneProduct ensembl:ENSG00000105221
ZNF746 GeneProduct ensembl:ENSG00000181220
NRF1 GeneProduct ensembl:ENSG00000106459
GUCY1A2 GeneProduct ensembl:ENSG00000152402
GAPDH GeneProduct ensembl:ENSG00000111640
PDE5 GeneProduct ensembl:ENSG00000138735 Inhibition of cGMP degradation by PDE5 increases cGMP availability [PMID:9714779].
PDE4A GeneProduct ensembl:ENSG00000065989
PDE4D GeneProduct ensembl:ENSG00000113448
GSK3B GeneProduct ensembl:ENSG00000082701
PPARGC1A GeneProduct ensembl:ENSG00000109819 Alternative name is PGC1A [uniprot:Q9UBK2]
PDE4C GeneProduct ensembl:ENSG00000105650
NOS1 GeneProduct ensembl:ENSG00000089250
PDE4B GeneProduct ensembl:ENSG00000184588
GUCY1B2 GeneProduct ensembl:ENSG00000123201
GUCY1A1 GeneProduct ensembl:ENSG00000164116 Also known as GUCY1A3 [uniprot:Q02108].
GUCY1B1 GeneProduct ensembl:ENSG00000061918 Also known as GUCY1B3 [uniprot:Q02153].
AKT3 GeneProduct ensembl:ENSG00000117020
NOS3 GeneProduct ensembl:ENSG00000164867 NOS3 is implicated in vascular smooth muscle relaxation through cGMP [PMID:1378832,PMID:20590592].
NOS2 GeneProduct ensembl:ENSG00000007171

References

  1. Molecular cloning of the cDNAs coding for the two subunits of soluble guanylyl cyclase from human brain. Giuili G, Scholl U, Bulle F, Guellaën G. FEBS Lett. 1992 Jun 8;304(1):83–8. PubMed Europe PMC Scholia
  2. Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD. J Biol Chem. 1992 Jul 25;267(21):14519–22. PubMed Europe PMC Scholia
  3. Cyclic nucleotide-dependent protein kinases. Scott JD. Pharmacol Ther. 1991;50(1):123–45. PubMed Europe PMC Scholia
  4. Nitric oxide and another potent vasodilator are formed from NG-hydroxy-L-arginine by cultured endothelial cells. Zembowicz A, Hecker M, Macarthur H, Sessa WC, Vane JR. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11172–6. PubMed Europe PMC Scholia
  5. Purification and characterization of a human NO synthase. Schmidt HH, Murad F. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1372–7. PubMed Europe PMC Scholia
  6. Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase. Livi GP, Kmetz P, McHale MM, Cieslinski LB, Sathe GM, Taylor DP, et al. Mol Cell Biol. 1990 Jun;10(6):2678–86. PubMed Europe PMC Scholia
  7. Endothelium-derived relaxing and contracting factors. Furchgott RF, Vanhoutte PM. FASEB J. 1989 Jul;3(9):2007–18. PubMed Europe PMC Scholia
  8. cGMP acts within cerebellar Purkinje cells to produce long term depression via mechanisms involving PKC and PKG. Hartell NA. Neuroreport. 1994 Mar 21;5(7):833–6. PubMed Europe PMC Scholia
  9. Characterization of cyclic nucleotide phosphodiesterases with cyclic GMP analogs: topology of the catalytic domains. Beltman J, Becker DE, Butt E, Jensen GS, Rybalkin SD, Jastorff B, et al. Mol Pharmacol. 1995 Feb;47(2):330–9. PubMed Europe PMC Scholia
  10. Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Virbasius JV, Scarpulla RC. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1309–13. PubMed Europe PMC Scholia
  11. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Br J Urol. 1996 Aug;78(2):257–61. PubMed Europe PMC Scholia
  12. Expression of mRNA for Akt, serine-threonine protein kinase, in the brain during development and its transient enhancement following axotomy of hypoglossal nerve. Owada Y, Utsunomiya A, Yoshimoto T, Kondo H. J Mol Neurosci. 1997 Aug;9(1):27–33. PubMed Europe PMC Scholia
  13. Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3’,5’-cyclic nucleotide phosphodiesterase. Loughney K, Hill TR, Florio VA, Uher L, Rosman GJ, Wolda SL, et al. Gene. 1998 Aug 17;216(1):139–47. PubMed Europe PMC Scholia
  14. Human soluble guanylate cyclase: functional expression and revised isoenzyme family. Zabel U, Weeger M, La M, Schmidt HH. Biochem J. 1998 Oct 1;335 ( Pt 1)(Pt 1):51–7. PubMed Europe PMC Scholia
  15. Phosphorylation of vasodilator-stimulated phosphoprotein: a consequence of nitric oxide- and cGMP-mediated signal transduction in brain capillary endothelial cells and astrocytes. Sporbert A, Mertsch K, Smolenski A, Haseloff RF, Schönfelder G, Paul M, et al. Brain Res Mol Brain Res. 1999 Apr 20;67(2):258–66. PubMed Europe PMC Scholia
  16. Immunohistochemical evidence for the NO cGMP signaling pathway in respiratory ciliated epithelia of rat. Zhan X, Li D, Johns RA. J Histochem Cytochem. 1999 Nov;47(11):1369–74. PubMed Europe PMC Scholia
  17. In vivo regulation of cell death by embryonic (pro)insulin and the insulin receptor during early retinal neurogenesis. Díaz B, Serna J, De Pablo F, de la Rosa EJ. Development. 2000 Apr;127(8):1641–9. PubMed Europe PMC Scholia
  18. The protooncogene TCL1 is an Akt kinase coactivator. Laine J, Künstle G, Obata T, Sha M, Noguchi M. Mol Cell. 2000 Aug;6(2):395–407. PubMed Europe PMC Scholia
  19. Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells. Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z. Arch Biochem Biophys. 2001 Oct 1;394(1):54–60. PubMed Europe PMC Scholia
  20. Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1. Künstle G, Laine J, Pierron G, Kagami Si S ichiro, Nakajima H, Hoh F, et al. Mol Cell Biol. 2002 Mar;22(5):1513–25. PubMed Europe PMC Scholia
  21. Regulation and co-ordination of nuclear gene expression during mitochondrial biogenesis. Goffart S, Wiesner RJ. Exp Physiol. 2003 Jan;88(1):33–40. PubMed Europe PMC Scholia
  22. Differential relaxing responses to particulate or soluble guanylyl cyclase activation on endothelial cells: a mechanism dependent on PKG-I alpha activation by NO/cGMP. Rivero-Vilches FJ, de Frutos S, Saura M, Rodriguez-Puyol D, Rodriguez-Puyol M. Am J Physiol Cell Physiol. 2003 Oct;285(4):C891-8. PubMed Europe PMC Scholia
  23. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Blount MA, Beasley A, Zoraghi R, Sekhar KR, Bessay EP, Francis SH, et al. Mol Pharmacol. 2004 Jul;66(1):144–52. PubMed Europe PMC Scholia
  24. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Takimoto E, Champion HC, Belardi D, Moslehi J, Mongillo M, Mergia E, et al. Circ Res. 2005 Jan 7;96(1):100–9. PubMed Europe PMC Scholia
  25. Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha. Borniquel S, Valle I, Cadenas S, Lamas S, Monsalve M. FASEB J. 2006 Sep;20(11):1889–91. PubMed Europe PMC Scholia
  26. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA, Martinez A, Santos A, et al. J Neurosci. 2007 May 23;27(21):5766–76. PubMed Europe PMC Scholia
  27. SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, et al. Genes Dev. 2008 Jan 15;22(2):252–64. PubMed Europe PMC Scholia
  28. The xanthine derivative KMUP-1 inhibits models of pulmonary artery hypertension via increased NO and cGMP-dependent inhibition of RhoA/Rho kinase. Chung HH, Dai ZK, Wu BN, Yeh JL, Chai CY, Chu KS, et al. Br J Pharmacol. 2010 Jun;160(4):971–86. PubMed Europe PMC Scholia
  29. PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson’s disease. Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, et al. Cell. 2011 Mar 4;144(5):689–702. PubMed Europe PMC Scholia
  30. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease. Taherzadeh-Fard E, Saft C, Akkad DA, Wieczorek S, Haghikia A, Chan A, et al. Mol Neurodegener. 2011 May 19;6(1):32. PubMed Europe PMC Scholia
  31. GAPDH binds to active Akt, leading to Bcl-xL increase and escape from caspase-independent cell death. Jacquin MA, Chiche J, Zunino B, Bénéteau M, Meynet O, Pradelli LA, et al. Cell Death Differ. 2013 Aug;20(8):1043–54. PubMed Europe PMC Scholia
  32. The AKT genes and their roles in various disorders. Cohen MM Jr. Am J Med Genet A. 2013 Dec;161A(12):2931–7. PubMed Europe PMC Scholia
  33. Modelling biochemical features of mitochondrial neuropathology. Bird MJ, Thorburn DR, Frazier AE. Biochim Biophys Acta. 2014 Apr;1840(4):1380–92. PubMed Europe PMC Scholia
  34. Mitochondrial Dysfunction and Calcium Dysregulation in Leigh Syndrome Induced Pluripotent Stem Cell Derived Neurons. Galera-Monge T, Zurita-Díaz F, Canals I, Hansen MG, Rufián-Vázquez L, Ehinger JK, et al. Int J Mol Sci. 2020 Apr 30;21(9):3191. PubMed Europe PMC Scholia
  35. Cooling Uncouples Differentially ROS Production from Respiration and Ca2+ Homeostasis Dynamic in Brain and Heart Mitochondria. Stevic N, Maalouf J, Argaud L, Gallo-Bona N, Lo Grasso M, Gouriou Y, et al. Cells. 2022 Mar 14;11(6):989. PubMed Europe PMC Scholia