title: Molecular analysis of erection regulatory factors in sickle cell disease associated priapism in the human penis.
abstract: OBJECTIVE
  Priapism is a vasculopathy that occurs in approximately 40% of patients with sickle cell disease. Mouse models suggest that dysregulated nitric oxide synthase and RhoA/ROCK signaling as well as increased oxidative stress may contribute to the mechanisms of sickle cell disease associated priapism. We examined changes in the protein expression of nitric oxide synthase and ROCK signaling pathways, and a source of oxidative stress, NADPH oxidase, in penile erectile tissue from patients with a priapism history etiologically related and unrelated to sickle cell disease.
  
  
  METHODS
  Human penile erectile tissue was obtained from 5 patients with sickle cell disease associated priapism and from 6 with priapism of other etiologies during nonemergent penile prosthesis surgery for erectile dysfunction or priapism management and urethroplasty. Tissue was also obtained from 5 control patients without a priapism history during penectomy for penile cancer. Samples were collected, immediately placed in cold buffer and then frozen in liquid nitrogen. The expression of phosphodiesterase 5, endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase, RhoA, ROCK1, ROCK2, p47(phox), p67(phox), gp91(phox) and β-actin were determined by Western blot analysis. Nitric oxide was measured using the Griess reaction.
  
  
  RESULTS
  In the sickle cell disease group phosphodiesterase 5 (p <0.05), endothelial nitric oxide synthase (p <0.01) and RhoA (p <0.01) expression was significantly decreased, while gp91(phox) expression (p <0.05) was significantly increased compared to control values. In the nonsickle cell disease group endothelial nitric oxide synthase, ROCK1 and p47(phox) expression (each p <0.05) was significantly decreased compared to control values. Total nitric oxide levels were not significantly different between the study groups.
  
  
  CONCLUSIONS
  Mechanisms of sickle cell disease associated priapism in the human penis may involve dysfunctional nitric oxide synthase and ROCK signaling, and increased oxidative stress associated with NADPH oxidase mediated signaling.
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Gwen
authors.initials: G
authors.lastname: Lagoda
authors.forename: Sena F
authors.initials: SF
authors.lastname: Sezen
authors.forename: Marcelo R
authors.initials: MR
authors.lastname: Cabrini
authors.forename: Biljana
authors.initials: B
authors.lastname: Musicki
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Burnett
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000503:physiopathology*; D011317:Priapism / Q000209:etiology*; D015398:Signal Transduction; D055815:Young Adult; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases