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Dysregulation of cG...
Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1 alpha
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- Bivalacqua, Trinity J. (författare)
- Brady Urological Institute, and Division of Cardiology, Department of Medicine Johns Hopkins Hospital
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- Kendirci, Muammer (författare)
- Department of Urology, Tulane University School of Medicine, New Orleans
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- Champion, Hunter C. (författare)
- Brady Urological Institute, and Division of Cardiology, Department of Medicine Johns Hopkins Hospital
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- Hellstrom, Wayne J. G. (författare)
- Department of Urology, Tulane University School of Medicine, New Orleans
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- Andersson, Karl-Erik (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Department of Clinical Pharmacology, Lund University Hospital, Lund
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- Hedlund, Petter (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Lund University Hospital
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(creator_code:org_t)
- 2007
- 2007
- Engelska.
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 99:6, s. 1488-1494
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1 beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1 alpha to the erectile compartment on erectile function in a rat model of diabetes. Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMV beta gal or AdCMVPKG1 alpha, 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. Compared to controls, AdCMV beta gal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1 alpha, 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 PKG1 alpha and PKG1 beta was lower in corporal tissue from DM AdCMV beta gal-transfected rats than in controls. PKG1 alpha expression was improved after AdCMVPKG1 alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1 alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. PKG1 alpha and PKG1 beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1 alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1 alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Nyckelord
- gene transfer
- corpus cavernosum
- diabetes
- nitric oxide
- cGMP
- corpus cavernosum; diabetes; gene transfer; nitric oxide; cGMP
- MEDICINE
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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