Phosphodiesterase type 5 in men with vasculogenic and post-radical prostatectomy erectile dysfunction: is there a molecular difference?

Serkan Karakus, Biljana Musicki, Arthur L. Burnett

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Objectives: To clarify the molecular basis of penile erection at the human level and distinguish the mechanisms underlying vasculogenic and post-radical prostatectomy (RP) erectile dysfunction (ED) subtypes. Patients and Methods: Erectile tissue was obtained from men without history of ED who underwent penile surgery for Peyronie's disease (control group, n = 5) and from men with ED who underwent penile prosthesis implantation (n = 17). ED was categorized into vasculogenic (n = 8) and post-RP (n = 9) subtypes. Penile erectile tissue samples were collected for molecular analyses of protein expressions of neuronal and endothelial isoforms of nitric oxide synthase (nNOS and eNOS, respectively), phospho-nNOS (Ser-1412), phospho-eNOS (Ser-1177), phospho-protein kinase B (Ser-473), phosphodiesterase type 5 (PDE5), α-smooth muscle actin, phospho-myosin phosphatase target subunit 1, RhoA/Rho-associated protein kinase (ROCK)-α, ROCK-β, 4-hydroxy-2-nonenal, and nNOS and eNOS uncoupling by Western blot. Results: Vasculogenic ED was characterized by decreased eNOS protein expression and eNOS and nNOS phosphorylation on their activatory sites (Ser-1177 and Ser-1412, respectively), uncoupled eNOS, upregulated PDE5 protein expression, increased ROCK activity, and increased oxidative stress in erectile tissue. Post-RP ED was characterized by decreased nNOS protein expression, increased nNOS phosphorylation on its activatory site (Ser-1412), uncoupled nNOS, downregulated PDE5 protein expression, and increased oxidative stress in erectile tissue. Conclusion: The mechanisms of vasculogenic and post-RP ED in the human penis involve derangements in constitutive nitric oxide synthase function, PDE5 protein expression and ROCK activity, and increased oxidative stress, which conceivably provide a molecular basis for chronically reduced nitric oxide bioavailability and increased smooth muscle contraction contributing to erectile impairment. Selective differences in PDE5 protein expression suggest distinct molecular mechanisms are in play for these ED subtypes.

Original languageEnglish (US)
Pages (from-to)1066-1074
Number of pages9
JournalBJU International
Volume122
Issue number6
DOIs
StatePublished - Dec 2018

Keywords

  • #erectiledysfunction
  • PDE-5 inhibitors
  • ROCK protein kinases
  • nitric oxide synthase
  • oxidative stress
  • phosphorylation
  • uncoupling

ASJC Scopus subject areas

  • Urology

Fingerprint

Dive into the research topics of 'Phosphodiesterase type 5 in men with vasculogenic and post-radical prostatectomy erectile dysfunction: is there a molecular difference?'. Together they form a unique fingerprint.

Cite this