Targeting soluble guanylyl cyclase in experimental Parkinsonism

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Inhibition of Striatal Soluble Guanylyl Cyclase-cGMP Signaling Reverses Basal Ganglia Dysfunction and Akinesia in Experimental Parkinsonism

OBJECTIVE There is clearly a necessity to identify novel non-dopaminergic mechanisms as new therapeutic targets for Parkinson's disease (PD). Among these, the soluble guanylyl cyclase (sGC)-cGMP signaling cascade is emerging as a promising candidate for second messenger-based therapies for the amelioration of PD symptoms. In the present study, we examined the utility of the selective sGC inhibi...

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Nucleotidyl cyclase activity of soluble guanylyl cyclase in intact cells.

Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and generates the second messenger cyclic GMP (cGMP). Recently, purified sGC α1β1 has been shown to additionally generate the cyclic pyrimidine nucleotides cCMP and cUMP. However, since cyclic pyrimidine nucleotide formation occurred only the presence of Mn(2+) but not Mg(2+), the physiological relevance of these in vitro findings...

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Soluble guanylyl cyclase activation promotes angiogenesis.

Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme carrying a heme prosthetic group that functions as a nitric oxide (NO) sensor. sGC is present in most cells types, including the vascular endothelium, where its biological functions remain largely unexplored. Herein, we have investigated the role of sGC in angiogenesis and angiogenesis-related properties of endothelial cells (EC). Initi...

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Nucleotidyl cyclase activity of recombinant soluble guanylyl cyclase

Background The ubiquitously expressed soluble guanylyl cyclase (sGC) converts guanosine 5'-triphosphate (GTP) to guanosine 3':5'-cyclic monophosphate (cGMP). The heterodimeric protein is activated by nitric oxide (NO). sGC plays a key role in the regulation of vascular tone and neurotransmission. Hence, sGC is an important target for the treatment of cardiovascular diseases e.g. pulmonary hyper...

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Regulation of soluble guanylyl cyclase by phosphorylation

Results In vitro kinase assays revealed that the α1, but not the β1, subunit of sGC is a PKG substrate and that the phosphorylation site is located within the first 360 residues of the α1. A constitutively active form of PKG stimulated incorporation of 32P into the α1 subunit in vivo. In addition, PKG could be detected in sGC immunoprecipitates, suggesting that the two proteins interact in cell...

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ژورنال

عنوان ژورنال: The FASEB Journal

سال: 2010

ISSN: 0892-6638,1530-6860

DOI: 10.1096/fasebj.24.1_supplement.lb467