Experimental priapism is associated with increased oxidative stress and activation of protein degradation pathways in corporal tissue

N. D. Kanika, A. Melman, Kelvin Davies

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Priapism is a debilitating disease for which there is at present no clinically accepted pharmacological intervention. It has been estimated that priapism lasting more than 24 h in patients is associated with a 44-90% rate of ED. In this investigation, we determined in two animal models of priapism (opiorphin-induced priapism in the rat and priapism in a mouse model of sickle cell disease) if there is evidence for an increase in markers of oxidative stress in corporal tissue. In both animal models, we demonstrate that priapism results in increased levels of lipid peroxidation, glutathione S-transferase activity and oxidatively damaged proteins in corporal tissue. Using western blot analysis, we demonstrated there is upregulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysosomal autophage protein, LC3. The antiapoptotic protein, Bcl-2, was also upregulated. Overall, we demonstrate that priapism is associated with increased oxidative stress in corporal tissue and the activation of protein degradation pathways. As oxidative stress is known to mediate the development of ED resulting from several etiologies (for example, ED resulting from diabetes and aging), we suggest that damage to erectile tissue resulting from priapism might be prevented by treatments targeting oxidative stress.

Original languageEnglish (US)
Pages (from-to)363-373
Number of pages11
JournalInternational Journal of Impotence Research
Volume22
Issue number6
DOIs
StatePublished - Nov 2010

Fingerprint

Priapism
Heat-Shock Proteins
Proteolysis
Oxidative Stress
glutaminyl-arginyl-phenylalanyl-seryl-arginine
Animal Models
Proteins
Ubiquitination
Sickle Cell Anemia
Ligases
Glutathione Transferase
Lipid Peroxidation
Up-Regulation
Western Blotting
Pharmacology

Keywords

  • lipid peroxidation
  • opiorphin
  • oxidative stress
  • priapism
  • sickle cell disease
  • ubiquination

ASJC Scopus subject areas

  • Urology

Cite this

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abstract = "Priapism is a debilitating disease for which there is at present no clinically accepted pharmacological intervention. It has been estimated that priapism lasting more than 24 h in patients is associated with a 44-90{\%} rate of ED. In this investigation, we determined in two animal models of priapism (opiorphin-induced priapism in the rat and priapism in a mouse model of sickle cell disease) if there is evidence for an increase in markers of oxidative stress in corporal tissue. In both animal models, we demonstrate that priapism results in increased levels of lipid peroxidation, glutathione S-transferase activity and oxidatively damaged proteins in corporal tissue. Using western blot analysis, we demonstrated there is upregulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysosomal autophage protein, LC3. The antiapoptotic protein, Bcl-2, was also upregulated. Overall, we demonstrate that priapism is associated with increased oxidative stress in corporal tissue and the activation of protein degradation pathways. As oxidative stress is known to mediate the development of ED resulting from several etiologies (for example, ED resulting from diabetes and aging), we suggest that damage to erectile tissue resulting from priapism might be prevented by treatments targeting oxidative stress.",
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