Linked Life Data

12222534

Source:http://linkedlifedata.com/resource/pubmed/id/12222534

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-9-10
pubmed:abstractText
Gene transfer to the penile corpora cavernosa of constructs of the inducible and endothelial nitric oxide synthase (NOS) cDNAs ameliorates erectile dysfunction in aged rats. In this study, we investigated whether the neuronal NOS (nNOS) variant responsible for erection, penile nNOS (PnNOS), can exert a similar effect, and whether the combination of electroporation with a helper-dependent adenovirus (AdV) improves gene transfer. PnNOS and beta-galactosidase cDNAs were cloned in plasmid (pCMV-PnNOS; pCMV-beta-gal) and "gutless" AdV (AdV-CMV-PnNOS; AdV-CMV-beta-gal) vectors, and injected into the penis of adult (beta-gal) or aged (PnNOS) rats, with or without electroporation. Penile erection was measured at different times after PnNOS cDNA injection, by electrical field stimulation of the cavernosal nerve. The expression of beta-galactosidase or PnNOS was estimated in penile tissue by either histochemistry and luminometry or Western blot, and the effects of AdV-CMV-PnNOS on mRNA expression were examined by a DNA microarray. We found that electroporation increased pCMV-beta-gal uptake, and its expression was detectable at 56 days. In the aged rats treated with pCMV-PnNOS and electroporation, the maximal intracavernosal:mean arterial pressure ratios were elevated for 11 and 18 days when compared with those in controls. Electroporation intensified penile uptake of as few as 10(6) viral particles (vp) of AdV-CMV-beta-gal, and with 10(7) vp beta-galactosidase was still detectable at 60 days. Electroporated AdV-CMV-PnNOS (10(7) vp) was effective at 18 days in stimulating the erection of aged rats, without inducing the expression of cytotoxic genes. In conclusion, intracavernosal gene therapy with PnNOS cDNA corrected the aging-related erectile dysfunction for at least 18 days when given by electroporation in a helper-dependent AdV at low viral loads.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-3363
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1033-41
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12222534-Adenoviridae, pubmed-meshheading:12222534-Aging, pubmed-meshheading:12222534-Animals, pubmed-meshheading:12222534-Blotting, Western, pubmed-meshheading:12222534-DNA, Complementary, pubmed-meshheading:12222534-Electric Stimulation, pubmed-meshheading:12222534-Electroporation, pubmed-meshheading:12222534-Erectile Dysfunction, pubmed-meshheading:12222534-Gene Expression, pubmed-meshheading:12222534-Gene Therapy, pubmed-meshheading:12222534-Genetic Vectors, pubmed-meshheading:12222534-Male, pubmed-meshheading:12222534-Nitric Oxide Synthase, pubmed-meshheading:12222534-Nitric Oxide Synthase Type I, pubmed-meshheading:12222534-Penile Erection, pubmed-meshheading:12222534-Penis, pubmed-meshheading:12222534-Plasmids, pubmed-meshheading:12222534-Rats, pubmed-meshheading:12222534-Rats, Inbred F344, pubmed-meshheading:12222534-beta-Galactosidase
pubmed:year
2002
pubmed:articleTitle
Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase.
pubmed:affiliation
Department of Urology, UCLA School of Medicine, Los Angeles, California 90509, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Corrected and Republished Article