Hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by hypoxia. The HIF-1 activation transduction pathway is poorly understood. In this report, we investigated the activation of extracellular regulated kinases (ERK) in hypoxia and their involvement in HIF-1 activation. We demonstrated that in human microvascular endothelial cells-1 (HMEC-1), ERK kinases are activated during hypoxia. Using dominant negative mutants, we showed that ERK1 is needed for hypoxia-induced HIF-1 transactivation activity. Moreover, using a kinase assay and Western blot experiments, we showed that HIF-1alpha is phosphorylated in hypoxia by an ERK-dependent pathway. These results evidence the role of mitogen-activated protein kinase in the transcriptional response to hypoxia.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0014-5793(00)01181-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.
Proc Natl Acad Sci U S A
February 2025
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158.
The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .
View Article and Find Full Text PDFFatty acid oxidation-induced HIF-1α activation facilitates hepatic urate synthesis through upregulating NT5C2 and XDH.
Life Metab
October 2024
CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai 200031, China.
Dyslipidemia affects approximately half of all people with gout, and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia (HU), but the underlying mechanisms remain elusive. We hypothesize that dyslipidemia promotes hepatic urate biosynthesis in HU and gout and fatty acid (FA) oxidation (FAO) drives this process. Here we developed a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU, gout, and normaluricemic controls.
View Article and Find Full Text PDFUnlabelled: The Sarm1 NAD hydrolase drives neurodegeneration in many contexts, but how Sarm1 activity is regulated remains poorly defined. Using CRISPR/Cas9 screening, we found loss of VHL suppressed Sarm1-mediated cellular degeneration. VHL normally promotes O -dependent constitutive ubiquitination and degradation of hypoxia-inducible factor 1 (HIF-1), but during hypoxia, HIF-1 is stabilized and regulates gene expression.
View Article and Find Full Text PDFHIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature.
Front Biosci (Landmark Ed)
January 2025
Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece.
Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy.
Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis.
Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells.
Int J Mol Sci
January 2025
Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondria, Oxidative Stress and Muscle Plasticity", Faculty of Medicine, University of Strasbourg, 67000 Strasbourg, France.
Peripheral blood mononuclear cells' (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of acute hypoxia on PBMC mitochondrial respiration and ROS production in healthy volunteers exposed to controlled oxygen reduction, achieving an inspired oxygen fraction of 10.5%.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!