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The hepatocyte growth factor (HGF)/c-Met signaling axis is deregulated in many cancers and plays important roles in tumor invasive growth and metastasis. An exclusively selective c-Met inhibitor (S)-6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (8) was
We have examined cyclic GMP concentrations, guanylate cyclase activities, and cyclic GMP phosphodiesterase (PDE) activities in developing retinas of congenic mice with different allelic combinations at the retinal degeneration (rd) and retinal degeneration slow (rds) loci. Although guanylate cyclase
OBJECTIVE
To screen the alpha-subunit of cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE6A) as a potential candidate gene for progressive retinal atrophy (PRA) in the Cardigan Welsh corgi dog.
METHODS
Single-strand conformation polymorphism (SSCP) analysis was used to screen short
The nucleotide (nt) sequence of the cDNA encoding the retinal rod cyclic 3'5'-GMP phosphodiesterase (PDE) alpha and gamma subunits from two strains of dogs-(i) Labrador Retrievers homozygous for autosomally recessively inherited rod-cone degeneration and (ii) the wild-type Beagle-are reported.
The retinal degeneration(rd) mouse is a commonly-studied animal model of the family of human-inherited retinal blindness known as retinitis pigmentosa, and is a likely model in which therapies for these conditions will continue to be developed and tested. Mutation of the beta-subunit of the rod
Cyclic GMP and its enzyme of metabolism, Phosphodiesterase, (PDE) appear to be involved in the normal processes of vision. An abnormality in the development of cyclic GMP PDE in the retina of the newborn Irish Setter dog also appears to be involved in at least one form of inherited retinal
The aim of the study was to develop an improved test to detect the codon 616 gene mutation in the alpha cyclic GMP phosphodiesterase gene that causes progressive retinal atrophy in the Cardigan Welsh Corgi. We studied 10 control dogs of known genotype at codon 616 of the alpha cyclic GMP
A degree of extractability and activation of cGMP-phosphodiesterase (PDE) (EC. 3.1.4.17) from the rod outer segment membranes was studied in Campbell rats with inherited retinal degeneration and control Wistar rats as compared to the control, the PDE extractability in the diseased rats was found to
A correlation was noted between alterations in activity of cGMP phosphodiesterase /PDE/ and in content of rhodopsin /R/ from rats of the Campbell strain with hereditary retina degeneration as well as from control animals of the Wistar strain. Dynamics of alterations in the PDE/R ratio was similar to
The beta subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE beta subunit in
Previous studies have shown that disruption of cyclic nucleotide metabolism by phosphodiesterase inhibitors and cyclic nucleotide analogues damages photoreceptors in rod-enriched retinae. In these studies the cone photoreceptors appeared damaged only after the surrounding rods had begun to
Cyclic nucleotides have been implicated in the differentiation and function of the vertebrate retina. In the normal retina of DBA mice, the specific activity of cyclic-nucleotide phosphodiesterase (PDE), with cyclic-AMP as the substrate (cAMP-PDE), increases eightfold between the 6th and 20th
Mice homozygous for the rd mutation display hereditary retinal degeneration and the classic rd lines serve as a model for human retinitis pigmentosa. In affected animals the retinal rod photoreceptor cells begin degenerating at about postnatal day 8, and by four weeks no photoreceptors are left.
Autosomal-dominant striatal degeneration (ADSD) is an autosomal-dominant movement disorder affecting the striatal part of the basal ganglia. ADSD is characterized by bradykinesia, dysarthria, and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present. Using
PF-04254644 is a selective kinase inhibitor of mesenchymal epithelial transition factor/hepatocyte growth factor receptor with known off-target inhibitory activity against the phosphodiesterase (PDE) family. Rats given repeated oral doses of PF-04254644 developed a mild to moderate myocardial