Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxia plays a fundamental role in the pathophysiology of common causes of mortality, including ischemic heart disease, stroke, cancer, chronic lung disease, and congestive heart failure. In these disease states, hypoxia induces changes in gene expression in target organs that either fail to result in adequate adaptation or directly contribute to disease pathogenesis. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that is expressed in response to cellular hypoxia and mediates multiple cellular and systemic homeostatic responses to hypoxia. Recent studies have provided evidence that important pathophysiological responses to hypoxia in pulmonary hypertension, myocardial ischemia, and cancer are mediated by HIF-1. Pharmacologic and gene therapy strategies designed to modulate HIF-1 activity may represent a novel and effective therapeutic approach to these common disorders.
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PMID:Hypoxia, HIF-1, and the pathophysiology of common human diseases. 1084 54

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates changes in gene expression in response to changes in cellular oxygen concentrations. HIF-1 is a heterodimer consisting of an oxygen-regulated HIF-1 alpha subunit and a constitutively expressed HIF-1 beta subunit. In mice, complete HIF-1 alpha deficiency results in embryonic lethality at midgestation because of cardiac and vascular malformations. Analyses of animal and cell culture models as well as human tissue have provided evidence that HIF-1 plays important roles in the pathophysiology of preeclampsia, intrauterine growth retardation, hypoxia-mediated pulmonary hypertension, and cancer. HIF-1 promotes neovascularization in response to myocardial or retinal ischemia by activating transcription of the gene encoding vascular endothelial growth factor. HIF-1 may also mediate the protective response to cerebral ischemia known as late-phase preconditioning.
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PMID:Hypoxia-inducible factor 1: control of oxygen homeostasis in health and disease. 1132 42

The cardiovascular and respiratory systems play key roles in O(2) homeostasis. Physiological responses to hypoxia involve changes in gene expression that are mediated by the transcriptional activator hypoxia-inducible factor (HIF)-1. Analysis of mice heterozygous for a knockout allele at the locus encoding the O(2)-regulated HIF-1alpha or HIF-2alpha subunit has revealed that these proteins are required for multiple physiological responses to chronic hypoxia, including erythrocytosis and pulmonary vascular remodeling. In mice with partial HIF-2alpha deficiency, hypoxia-induced expression of endothelin-1 and norepinephrine is dramatically impaired, and the mice fail to develop pulmonary hypertension after 4 wk of exposure to 10% O(2). In mice with partial HIF-1alpha deficiency, the ability of the carotid body to sense and/or respond to acute or chronic hypoxia is lost. In wild-type mice, brief episodes of intermittent hypoxia are sufficient to induce production of erythropoietin (EPO), which protects the heart against apoptosis after ischemia-reperfusion, whereas in mice with partial HIF-1alpha deficiency, intermittent hypoxia does not induce EPO production or cardiac protection. Parenteral administration of EPO to rodents is sufficient to induce dramatic protection against ischemia-reperfusion injury in the heart. Thus HIF-1 mediates critical physiological responses to hypoxia, and the elucidation of these homeostatic mechanisms may lead to novel therapies for the most common causes of mortality in the US population.
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PMID:O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1. 1476 67

Pulmonary hypertension (PH) is a clinically common malignant cardiovascular disease. Pyroptosis is a new form of inflammatory cell death that is involved in many disease processes. Glioma-associated oncogene family zinc finger 1 (GLI1) is a transcriptional activator that participates in many diseases, but its role has never been explored in inducing pyroptosis and the progress of PH. In this study, we used an animal model and cell molecular biology to determine the effect of GLI1 on chronic hypoxia-mediated PH progression and pulmonary artery smooth muscle cell (PASMC) pyroptosis. The major findings of the present study are as follows: Hypoxia induced aberrant expression of GLI1. The inhibition of GLI1 attenuated hypoxia-induced PH and PASMC pyroptosis. Meanwhile, GLI1 enhanced apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression by binding with its promoter. GLI1 may promote PASMC pyroptosis through ASC to affect the progression of PH. These findings may identify novel targets for molecular therapy of PH.
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PMID:GLI1-mediated pulmonary artery smooth muscle cell pyroptosis contributes to hypoxia-induced pulmonary hypertension. 3186 9