Disease relevance of Hif1a

• HIF-1alpha mRNA staining was poorly positive in control, hypoxia for 3 and 7 d, but enhanced significantly after 14 d of hypoxia (0.20 +/- 0.02, P<0.05), then remained stable [1].
• Hypoxia inducible factor-1 alpha correlated the expression of heme oxygenase 1 gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension [1].
• Steady-state levels of HIF-1alpha protein were stimulated by 15 min of ischemia and showed a 2-fold increase at 30 min and 1, 3, and 6 h [2].
• Sex-related dimorphic response of HIF-1 alpha expression in myocardial ischemia [3].
• HIF-1alpha protein was also elevated by experimental torsion and reperfusion compared with normoxic controls [2].

Psychiatry related information on Hif1a

• RESULTS: When the period of alcohol consumption increased, the positive rate of expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) mRNA was more significantly elevated in the liver of the alcohol group than in the control group (P</=0.05) [4].

High impact information on Hif1a

• After 24 h of 10% O(2), Spalax Epo reaches its maximal expression, remarkably 6-fold higher than the maximum in Rattus; (ii) the HIF-1 alpha level in normoxia is 2-fold higher in Spalax than in Rattus [5].
• Interestingly, NGF effect was specific for HIF-2 alpha mRNA because it did not affect HIF-1 alpha mRNA levels [6].
• METHODS: We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1 alpha gene expression [7].
• Nix, a hypoxia-sensitive member of the Bcl-2 family, is upregulated at the mRNA level during hypoxia through induction of a hypoxia-inducible factor-1 alpha (HIF-1 alpha) response element in its promoter sequence [8].
• Identification of potential stroke targets by lentiviral vector mediated overexpression of HIF-1 alpha and HIF-2 alpha in a primary neuronal model of hypoxia [9].

Chemical compound and disease context of Hif1a

• HIF-1 alpha and HLF/EPAS are two basic helix-loop-helix/PAS domain transcription factors that bind to hypoxia sensitive elements in the promoters /enhancers of hypoxia sensitive genes such as vascular endothelial growth factor (VEGF) [10].
• HIF-1 alpha mRNA expression is increased by phorbol myristate acetate but not by anoxia or cobalt [10].
• Adenoviral infection of cultures of cardiac myocytes with the facilitative glucose transporter, GLUT1 followed by hypoxia of 24h also resulted in a significant reduction in the protein expression of HIF-1alpha compared to control vector-infected cultures [11].
• CONCLUSIONS: Since it is doubtful whether dephosphorylation of amifostine to the active metabolite WR-1065 occurs within tumoral tissues (an acidic environment that lacks vascular alkaline phosphatase activity), intracellular hypoxia and upregulation of HIF1 alpha represents an additional, normal tissue-specific, amifostine cytoprotective pathway [12].
• The effects of L-arginine on neurological function, histopathology, and expression of hypoxia-inducible factor-1 alpha following spinal cord ischemia in rats [13].

Biological context of Hif1a

• Inhibition of COX-2 activities would prevent vHL protein from degradation and suppress HIF-1alpha up-regulation [14].
• Cardiac protection induced by intermittent hypoxia is critically dependent on Hif1a gene dosage [15].
• In addition, glucose uptake and glycolysis resulted in substantial decreased levels of p53, which is regulated by HIF-1alpha [11].
• MDA468 breast tumor cell lines were incubated with a high amifostine concentration (10 m M) to overcome the natural resistance of cancer cells to influx of the non-hydrolyzed WR-2721, and the HIF1 alpha protein levels were determined by Western blot analysis [12].
• Similarly, interrupting the respiratory chain with potassium cyanide reversed the excitatory effect of IL-1 beta on HIF-1 alpha nuclear translocation and activation [16].

Anatomical context of Hif1a

• In pulmonary arterial tunica media, the levels of HIF-1alpha protein were markedly up-regulated after 3 d and 7 d of hypoxia (0.20 +/- 0.02; 0.22 +/- 0.02, P<0.05), then declined after 14 d and 21 d of hypoxia [1].
• HIF-1alpha protein in control was poorly positive (0.05 +/- 0.01), but was up-regulated in pulmonary arterial tunica intima of all hypoxic rats [1].
• To examine the effects of ischemia on HIF-1alpha mRNA and protein expression in the testis, rats were subjected to unilateral testicular ischemia by placing a ligature around spermatic artery or ischemia-inducing experimental torsion and reperfusion [2].
• HIF-1alpha mRNA showed equal expression in testis, all segments of epididymis, ductus deferens, accessory sex glands, and penis [2].
• Transient expression of hypoxia-inducible factor-1 alpha and target genes in peripheral nerves from diabetic rats [17].

Associations of Hif1a with chemical compounds

• Angiotensin II induces hypoxia-inducible factor-1 alpha in PC 12 cells through a posttranscriptional mechanism: role of AT2 receptors [18].
• Preliminary evidence suggests that this effect of vitamin A involves increased mRNA levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) [19].
• Cardiac expressions of HIF-1 alpha and HLF/EPAS, two basic loop helix/PAS domain transcription factors involved in adaptative responses to hypoxic stresses [10].
• The increase in HIF-1alpha in diabetic nerves coincided with a similarly transient increase in the expression of several HIF-1alpha target genes including vascular endothelial growth factor, lactate dehydrogenase and erythropoietin, which subsided 8-10 weeks after induction of diabetes [17].
• This result suggested that glucose induces HIF-1alpha degradation via a proteasomal pathway [11].

Regulatory relationships of Hif1a

• Finally, they suggest that protein kinase C may prime hypoxia induced gene regulation by inducing expression of HIF-1 alpha mRNAs [10].

Other interactions of Hif1a

• To date, virtually nothing is known about the signaling pathways that lead to either EPAS1 or HIF1-alpha activation [20].
• Linear correlation analysis showed that HIF-1alpha mRNA, HO-1 protein and mPAP were associated with pulmonary remodeling [1].
• A reduction in SM-20/PHD3 mRNA expression paralleled the increase in HIF-1 alpha [18].
• Linear correlation analysis showed that iNOS protein was associated with both mean pulmonary arterial pressure (r = 0.74, P < 0.01) and hypoxic pulmonary vascular remodeling (r = 0.78, P < 0.01), whereas the inverse was associated with HIF-1alpha protein (r = -0.52, P < 0.01) [21].
• HIF-1alpha protein was detected by immunoblot analysis of nuclear protein extracts from normoxic testes [2].

Analytical, diagnostic and therapeutic context of Hif1a

• Gel shift analysis revealed that ANG-II-induced nuclear HIF-1 alpha protein binds to consensus sites [18].
• Real-time PCR failed to show a significant increase in HIF-1 alpha transcripts after ANG II challenge at any time point [18].
• We studied expressions of hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha), an activator of the VEGF gene, and VEGF by reverse transcriptase-polymerase chain reaction, Western blotting, and immunostaining [22].
• RT-PCR revealed that HIF-1alpha mRNA expression at all times of ischemic treatment and reperfusion was unchanged compared with normoxic controls [2].
• Male and female rats were euthanized 5 and 24 h after coronary ligation (M-MI and F-MI; MI, myocardial ischemia), and HIF-1 alpha expression was determined by immunohistochemistry, Western blot, and quantitative RT-PCR [3].

References