RGD Reference Report - Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1alpha. - Rat Genome Database

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Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1alpha.

Authors: Bivalacqua, TJ  Kendirci, M  Champion, HC  Hellstrom, WJ  Andersson, KE  Hedlund, P 
Citation: Bivalacqua TJ, etal., BJU Int. 2007 Jun;99(6):1488-94. Epub 2007 Mar 12.
RGD ID: 7775062
Pubmed: PMID:17355372   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1464-410X.2007.06794.x   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
impotence  ISOPrkg1 (Rattus norvegicus)7775062; 7775062associated with Diabetes Mellitus more ...RGD 
impotence  IEP 7775062associated with Diabetes Mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkg1  (protein kinase cGMP-dependent 1)

Genes (Mus musculus)
Prkg1  (protein kinase, cGMP-dependent, type I)

Genes (Homo sapiens)
PRKG1  (protein kinase cGMP-dependent 1)


Additional Information