The sequential activation and repression of the human PDGF-B gene during chronic hypoxia reveals antagonistic roles for the depletion of oxygen and glucose.
Transfection of MKN28 cells with a dominant-negative PKC-epsilon blocked the induction of GRP78 through ERK by hypoxia, indicating that PKC-epsilon directly participated in GRP78 induction under hypoxia.
Also, introduction of an antisense oligonucleotide for Egr-1 diminishes EGFR expression during hypoxia, indicating that the up-regulation of EGFR by hypoxia is mediated through Egr-1.
Primary meningioma cell cultures were established and cell culture experiments were performed using a hypoxia chamber to stimulate HIF-1alpha and VEGF production.
First, HIF-1 controls the expression of gene products that stimulate angiogenesis, such as vascular endothelial growth factor, and promote metabolic adaptation to hypoxia, such as glucose transporters and glycolytic enzymes, thus providing a molecular basis for involvement of HIF-1 in tumor growth and angiogenesis.
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that regulates transcriptional activation of several genes that are responsive to oxygen lack, including erythropoietin, vascular endothelial growth factor, various glycolytic enzymes and the GLUT-1 glucose transporter.
Transfection experiments in HepG2 cells showed that both hypoxia and overproduction of HIF-1alpha specifically repressed the transcriptional activity of the rat afp regulatory region through the sequence 5'-CACGTGGG-3' located at -3625 to -3619.
Gel shift assays with a (32)P-labeled leptin promoter -116/HRE probe and nuclear extracts from hypoxia-treated cells indicated binding of the HIF1alpha/beta heterodimer, which was blocked with an excess of unlabeled -116/HRE probe or a HIF1-binding probe from the erythropoietin gene enhancer.
Overexpression of HIF-1alpha and HIF-2alpha was demonstrated in three HNSCC cell lines under hypoxia and tumor tissue versus normal tissue (n = 20, HIF-1alpha, P = 0.023; HIF-2alpha, P = 0.013).
The results showed that, although hypoxia markedly increased ROS generation in HeEB1 cells but not in EB8 cells, EB8 cells showed essentially a normal response to hypoxia, as assessed by VEGF gene promoter activity, HIF-1alpha accumulation, and HIF-1 target gene expressions.
In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.
In vivo, basal membrane GLUT1 is upregulated over gestation, increased in diabetic pregnancy, and decreased in chronic hypoxia, while microvillous membrane GLUT1 is unaffected.
Although the DN patients have inappropriately low EPO levels for the severity of their anaemia, they can mount an appropriate EPO response to moderate hypoxia.
Taken together, our in-vivo results do not support a gross modulatory effect of a short-term treatment with radical scavenging agents on EPO-production during or after hypoxia in humans, as derived from the detected changes of MDA-concentrations in peripheral plasma.
Serum erythropoietin concentration increased significantly from 9.5 +/- 3.51 to 33.6 +/- 11.64 U L(-1) (P < 0.05) after 2 days of hypoxia.Thereafter, s-[epo] decreased.
We hypothesize that the mechanism of Cap43 overexpression in cancer cells involves a state of hypoxia characteristic of cancer cells where the Cap43 protein becomes a signature for this hypoxic state.
Cyclooxygenase-2 and presenilin-1 gene expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells.
These data demonstrate that PGE(2) production via COX-2-catalyzed pathway plays a critical role in HIF-1alpha regulation by hypoxia and imply that COX-2 inhibitors can prevent hypoxic induction of HIF-mediated gene transcription in cancer cells.
Combined treatment of hypoxia and TGF-beta1 caused a significant increase in TGF-beta1 (37%; P < 0.05), TGF-beta2 (12%; P < 0.05), TGF-betaIR (32%; P < 0.05) and TGF-betaIIR (34%; P < 0.05).