liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1alpha.
Brady Urological Institute, and Division of Cardiology, Department of Medicine Johns Hopkins Hospital.
Department of Urology, Tulane University School of Medicine, New Orleans.
Brady Urological Institute, and Division of Cardiology, Department of Medicine Johns Hopkins Hospital.
Department of Urology, Tulane University School of Medicine, New Orleans.
Show others and affiliations
2007 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 99, no 6, 1488-1494 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1alpha to the erectile compartment on erectile function in a rat model of diabetes.

MATERIALS AND METHODS: Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMVbetagal or AdCMVPKG1alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control.

RESULTS: Compared to controls, AdCMVbetagal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1alpha and PKG1beta was lower in corporal tissue from DM AdCMVbetagal-transfected rats than in controls. PKG1alpha expression was improved after AdCMVPKG1alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control.

CONCLUSION: PKG1alpha and PKG1beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.

Place, publisher, year, edition, pages
2007. Vol. 99, no 6, 1488-1494 p.
Keyword [en]
corpus cavernosum; diabetes; gene transfer; nitric oxide; cGMP
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-77899DOI: 10.1111/j.1464-410X.2007.06794.xPubMedID: 17355372OAI: oai:DiVA.org:liu-77899DiVA: diva2:529774
Available from: 2012-05-31 Created: 2012-05-31 Last updated: 2017-12-07

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Hedlund, Petter

Search in DiVA

By author/editor
Hedlund, Petter
In the same journal
BJU International
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 46 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf