Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that cyclic guanosine-3',5'-monophosphate (cGMP) protects spinal motor neurons against acute reactive oxygen species (ROS)-induced toxicity but not against chronic ROS-induced or glutamate (Glu)-induced toxicity. In this study, we investigated the effects of phosphodiesterase (PDE) inhibitors on the survival of cultured spinal motor neurons. Selective PDE5 inhibitors (dipyridamole, T-1032, and zaprinast) as well as a nonselective PDE inhibitor (aminophylline) protected motor and nonmotor neurons against both acute ROS-induced and chronic Glu-induced neurotoxicity, whereas selective inhibitors of PDE1-4 offered no protection. 8-Bromo-cGMP (8br-cGMP), a cGMP analogue, protected both motor and nonmotor neurons against acute ROS-induced toxicity but protected only nonmotor neurons against chronic Glu-induced toxicity. This neuroprotection was blocked by KT5823, a cGMP-dependent protein kinase (PKG) inhibitor. Immunohistochemical staining confirmed that PDE5 and PKG are located in almost all rat lumbar spinal neurons. Furthermore, semiquantitative analysis of the immunostaining intensity revealed that PDE5 was more abundant in motor neurons than in nonmotor neurons. Our results suggest that this difference in the amount of PDE5 may be responsible for the vulnerability of motor neurons to chronic excitotoxicity. In addition, the results of this study raise the possibility that PDE5 inhibitors might be used as a treatment for amyotrophic lateral sclerosis.
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PMID:Phosphodiesterase inhibitors are neuroprotective to cultured spinal motor neurons. 1254 4

The Kinetworks trade mark multi-immunoblotting technique was used to evaluate the expressions of 78 protein kinases, 24 protein phosphatases and phosphorylation states of 31 phosphoproteins in thoracic spinal cord tissue from control subjects and patients having the sporadic form of amyotrophic lateral sclerosis (ALS). In both the cytosolic (C) and particulate (P) fractions of spinal cord from ALS patients as compared with controls, there were increased levels of calcium/calmodulin-dependent protein kinase kinase (CaMKK; C = 120% increase/P = 580% increase;% change, compared with control), extracellular regulated kinase 2 (ERK2; C = 120% increase/P = 170% increase), G protein-coupled receptor kinase 2 (GRK2; C = 140% increase/P = 140% increase), phospho-Y279/216 glycogen synthase kinase 3 alpha/beta (GSK3alpha/beta; C = 90% increase/P = 220% increase), protein kinase B alpha (PKBalpha; C = 360% increase/P = 200% increase), phospho-T638 PKCalpha/beta (C = 630% increase/P = 170% increase), cGMP-dependent protein kinase (PKG; C = 100% increase/P = 75% increase), phospho-T451 dsRNA-dependent protein kinase (PKR; C = 2600% increase/P = 3330% increase), ribosomal S6 kinase 1 (RSK1; C = 750% increase/P = 630% increase), phospho-T389 p70 S6 kinase (S6K; C = 1000% increase/P = 460% increase), and protein-tyrosine phosphatase 1 delta (PTP1delta; C = 43% increase/P = 70% increase). Cytosolic increases in phospho-alpha-S724/gamma-S662 adducin (C = 15650% increase), PKCalpha (C = 100% increase) and PKCzeta (C = 190% increase) were found in ALS patients as compared with controls, while particulate increases in cAMP-dependent protein kinase (PKA; 43% increase), protein kinase C beta (PKCbeta; 330% increase), and stress-activated protein kinase beta (SAPKbeta; 34% increase) were also observed. Cyclin-dependent kinase-associated phosphatase (KAP) was apparently translocated, as it was reduced (31% decrease) in cytosolic fractions but elevated (100% increase) in particulate fractions of ALS spinal cord tissue. Our observations indicate that ALS is associated with the elevated expression and/or activation of many protein kinases, including PKCalpha, PKCbeta, PKCzeta and GSK3alpha/beta, which may augment neural death in ALS, and CaMKK, PKBalpha, Rsk1, S6K, and SAPK, which may be a response to neuronal injury that potentially can mitigate cell death.
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PMID:Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord. 1267 19

Background. Rhubarb, a traditional Chinese medicine, promotes viscera and remove blood stasis. Rhubarb is skilled in smoothening meridians, improving blood circulation which exhibits better efficacy on cerebral ischemic stroke. In this study, we aimed to analyze the underlying mechanisms of rhubarb which treated rats of middle cerebral artery occlusion (MCAO) model according to an iTRAQ-based proteomics and bioinformatics analysis. 30 rats were randomly allocated into three groups including sham group (SG), model group (MG), and rhubarb group (RG). Rhubarb group was given a gavage of rhubarb decoction at dose of 3 g/kg and the remaining groups were prepared with normal saline by gavage. Rats from MG and RG were induced into MCAO model. The effects of rhubarb were estimated by Modified Neurological Severity Score (mNSS) and cerebral infarct volume. The brain tissues were measured via the quantitative proteomic approach of iTRAQ coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, the bioinformatics analysis of overlapping differentially expression proteins (DEPs) was conducted by DAVID, KEGG, and Cytoscape. Specific selective DEPs were validated by Western blotting. Rats treated with rhubarb after MCAO showed a significant reduction on mNSS and cerebral infarct volume compared with MG. In MG versus SG and RG versus MG, we identified a total of 4578 proteins, of which 287 were DEPs. There were 76 overlapping DEPs between MG versus SG and RG versus MG. Through bioinformatics analysis, 14 associated pathways were searched including cGMP-PKG signaling pathway, tuberculosis, synaptic vesicle cycle, amyotrophic lateral sclerosis, long-term potentiation, and so on. 76 overlapping DEPs mainly involved synaptic vesicle cycling biological processes based on GO annotation. Further, the selective overlapping DEPs were verified at the protein level by using Western blotting. Our present study reveals that rhubarb highlights promising neuroprotective effect. Rhubarb exerts novel therapeutic action via modulating multiple proteins, targets, and pathways.
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PMID:iTRAQ-Based Proteomics Analysis Reveals the Effect of Rhubarb in Rats with Ischemic Stroke. 3011 17