Short-cycle hypoxia in the intact heart: hypoxia-inducible factor 1alpha signaling and the relationship to injury threshold
| Autor: | Xue Han Ning, Norman E. Buroker, Shi Han Chen, Min Zhang, Outi M. Hyyti, Michael A. Portman, Shu Ping Li, Fu Ren Li, De Song Song, Ming Ge, Cheng Su Xu |
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| Rok vydání: | 2006 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Time Factors Physiology Biology Lesion chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Hypoxia chemistry.chemical_classification Myocardium Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Heme oxygenase Vascular endothelial growth factor Oxygen Enzyme Endocrinology chemistry Hypoxia-inducible factors Circulatory system Rabbits medicine.symptom Signal transduction Cardiology and Cardiovascular Medicine Cardiomyopathies Signal Transduction |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 292(1) |
| ISSN: | 0363-6135 |
| Popis: | Hypoxia-inducible factor 1α (HIF-1α) transcriptionally activates multiple genes, which regulate metabolic cardioprotective and cross-adaptive mechanisms. Hypoxia and several other stimuli induce the HIF-1α signaling cascade, although little data exist regarding the stress threshold for activation in heart. We tested the hypothesis that relatively mild short-cycle hypoxia, which produces minimal cardiac dysfunction and no sustained or major disruption in energy state, can induce HIF-1α activation. We developed a short-cycle hypoxia protocol in isolated perfused rabbit heart to test this hypothesis. By altering cycling conditions, we identified a specific cycle with O2 content and duration that operated near a threshold for causing functional injury in these rabbit hearts. Mild short-cycle hypoxia for 46 min elevated HIF-1α mRNA and protein within 45 min after reoxygenation. Expression also increased for multiple HIF-1α target genes, such as VEGF and heme oxygenase 1. After mild hypoxia, VEGF protein accumulation occurred, although HIF-1α and VEGF protein accumulation were suppressed after more severe hypoxia, which also caused depletion of ATP and nondiffusible nucleotides. In summary, these results indicate that mild near-threshold hypoxia induces HIF-1α cascade, but more severe hypoxia suppresses protein accumulation for this transcription factor and the target genes. Posttranscriptional suppression of these proteins occurs under conditions of altered energy state, exemplified by ATP depletion. |
| Databáze: | OpenAIRE |
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