Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein product of the retinoblastoma susceptibility gene, RB, is a nuclear phosphoprotein that modulates transcription of genes involved in growth control via interactions with transcription factors. Renin is a rate-limiting enzyme of the renin-angiotensin system that regulates blood pressure and water-electrolyte balance. Renin gene expression is regulated in a tissue-specific and developmentally linked manner. Similarly, the expression of RB is controlled in a differentiation-linked manner. Thus, to investigate whether RB is involved in the regulation of renin gene expression, we examined the effects of RB on transcriptional activity of the mouse renin (Ren-1C) promoter. The Ren-1C promoter contains two transcriptionally important elements; the RU-1 (-224 to -138) and RP-2 (-75 to -47) elements. RB activated the Ren-1C promoter in human embryonic kidney cells. The promoter element responsible for RB-mediated transcriptional regulation was the RP-2 element. The results of DNA-protein binding experiments showed that RB increased nuclear binding activity to the RP-2 element, and site-directed mutation which disrupted binding of nuclear factors to the RP-2 element markedly reduced RB-mediated activation of Ren-1C promoter in human embryonic kidney cells. These results indicate that the RP-2 element plays an important role in RB-mediated transcriptional regulation of Ren-1C promoter activity in human embryonic kidney cells, thereby suggesting an interesting mechanism by which RB may modulate the renin-angiotensin system.
 ...
PMID:A novel proximal element mediates the regulation of mouse Ren-1C promoter by retinoblastoma protein in cultured cells. 920 91

There is currently intense interest in the development of gene therapy for cardiovascular disease. The stimulation of therapeutic angiogenesis for ischemic heart disease has been one of the areas of greatest promise. Encouraging results have been obtained with the angiogenic cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor in animal models, leading to clinical trials in ischemic heart disease. VEGF also has therapeutic potential in a second area of cardiovascular gene therapy, the enhancement of arterioprotective endothelial functions to prevent postangioplasty restenosis and bypass graft arteriopathy. The endothelial cell growth and survival functions of VEGF promote endothelial regeneration, whereas VEGF-induced endothelial production of NO and prostacyclin inhibits vascular smooth muscle cell proliferation. Inhibition of neointimal hyperplasia may also be achieved by gene transfer of endothelial NO synthase (eNOS), PGI synthase, or cell cycle regulators (retinoblastoma, cyclin or cyclin-dependent kinase inhibitors, p53, growth arrest homeobox gene, fas ligand) or antisense oligonucleotides to c-myb, c-myc, proliferating cell nuclear antigen, and transcription factors such as nuclear factor kappaB and E2F. An improved understanding of etiologically complex pathologies involving the interplay of genes and the environment, such as atherosclerosis and systemic hypertension, has led to the identification of new targets for gene therapy, with the potential to alleviate inherited genetic defects such as familial hypercholesterolemia. The use of vasodilator gene overexpression and antisense knockdown of vasoconstrictors to reduce blood pressure in animal models of systemic and pulmonary hypertension offers the prospect of gene therapy for human hypertensive disease. The renin-angiotensin system has been the target of choice for antihypertensive strategies because of its wide distribution and additional effects on fibrinolytic and oxidative stress pathways. Gene therapy in cardiovascular disease has an exciting future but remains at an early stage. Further developments in gene transfer vector technology and the identification of additional target genes will be required before its full therapeutic potential can be realized.
 ...
PMID:Gene therapy for cardiovascular disease: a case for cautious optimism. 1171 25

Various stresses on the heart, such as myocardial infarction and hemodynamic overload, activate the sympathetic nervous system and the renin-angiotensin system, ultimately reach the nuclei of cardiomyocytes, and change the pattern of gene expression associated with cardiac hypertrophy. Although present pharmacological therapy for heart failure targets such extracellular molecules, mortality due to heart failure is still high. A zinc finger protein, GATA4, is one of the hypertrophy-responsive transcription factors, forms a functional protein complex with an intrinsic histone acetyltransferase, p300, and regulates pathological cardiac hypertrophy. Disruption of this complex results in the inhibition of cardiac hypertrophy and heart failure in vivo. To establish a more effective therapy for heart failure, we have been analyzing a common nuclear pathway within cardiomyocytes. We identified 73 GATA4 binding proteins by tandem-affinity purification and mass spectrometric analysis. Noble GATA4 binding partners, such as cyclin-dependent kinase-9 (Cdk9: the core factor of positive transcription elongation factor b) and retinoblastoma-association protein 48/46 (RbAp48/46: the co-repressor complexes containing HDAC1/2), regulate the p300/GATA4-mediated signaling pathway and hypertrophic responses. Further analysis of p300/GATA4 complex is expected to identify target molecules for heart failure therapy.
 ...
PMID:[Functional Analysis of GATA4 Complex, a Cardiac Hypertrophy-response Transcriptional Factor, Using a Proteomics Approach]. 2683 85