Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasopressin is actively involved in the regulation of blood pressure to the same degree as catecholamines and the renin angiotensin aldosterone system are, especially in stressful situations. Vasopressin induces and increase in blood pressure when mechanisms buffering its potent vasoconstrictor effect are altered. Vasopressin binds to specific membrane receptors classified into two main types. The V1 receptors found in blood vessels, platelets and hepatocytes are linked to two intra-cellular messengers, namely 1,2 diacylglycerol and 1,4,5 inositol triphosphate which stimulate protein kinase C and calcium-calmodulin kinase in the presence of calcium. V2-renal receptors stimulate the production of cyclic AMP which activates protein kinase A. Subsequently, the actin network is altered and particles containing pores agregate at the cell surface to produce water molecules reabsorption. Vasopressin modifies human hemostasis via platelet aggregation, stimulation of the three fractions of factor VIII, of factor XII and of fibrinopeptide A. These properties were used to treat hemostasis abnormalities seen in Von Willebrand's disease and hemophilia. There is a feed-back loop between vasopressin and the atrial natriuretic factor: vasopressin stimulates atrial natriuretic factor release via a V1 action whereas the atrial natriuretic factor reduces vasopressin release and inhibits vasopressin antidiuretic action.
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PMID:[Vasopressin, the antidiuretic hormone]. 295 73

Considering the plasticity of hematopoietic stem cells (HSC), they would be ideal targets for gene therapy of hemophilia A by virtue of their progeny providing immediate access to the bloodstream. However, several attempts to show expression of recombinant factor VIII (rFVIII) by primary hematopoietic cells and cell lines have failed; this failure was attributed to the inability of HSC to secrete rFVIII. Here we describe the generation of stable, FVIII-secreting hematopoietic cell lines representing different blood-cell types using a bicistronic lentiviral vector encoding for a B-domain-deleted FVIII (FVIII Delta B) and enhanced green fluorescence protein (EGFP). Transduced cell lines with erythroid and/or megakaryocytic background, (K562-F8 and TF-1-F8) secrete high levels of FVIII in the order of 76.4 and 41.6 ng FVIII:C/ml, whereas moderate and low levels are observed in B lymphoblastoid Raji-F8 cells and the T leukemia line Jurkat-F8 which secrete 6.73 and 1.83 ng FVIII:C/ml, respectively. The capacity to secrete rFVIII appeared to depend on factors related to the cell lineage rather than on the transduction efficacy. Stimulation of transduced cells with the protein kinase C (PKC)-activator phorbol myristate acetate (PMA) resulted in a marked augmentation of rFVIII secretion and enhanced green fluorescent protein (EGFP). Incubation with 0.1 and 1 ng/ml PMA resulted in up to 2.7-fold (K562-F8, Raji-F8) and 1.8-fold (293T-F8) increased rFVIII secretion. The established cell lines should be helpful in further elucidating mechanisms that are able to improve FVIII secretion in hematopoietic cells on a post-translational level and suggest reanalysis of hematopoietic cells as target for gene therapy of hemophilia.
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PMID:Generation and characterization of human hematopoietic cell lines expressing factor VIII. 1220 58