Hydrogen sulphide induces HIF-1α and Nrf2 in THP-1 macrophages
| Autor: | Thomas Erker, Michael Hintersteininger, Bernhard M.K. Gmeiner, Hilde Laggner, Lilian Lohninger, Monika Praschberger, Lenka Tomasova |
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| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
MAP Kinase Signaling System NF-E2-Related Factor 2 p38 mitogen-activated protein kinases Inflammation Biology Biochemistry chemistry.chemical_compound Western blot Cell Line Tumor medicine Humans Hydrogen Sulfide Protein kinase A Transcription factor Dose-Response Relationship Drug medicine.diagnostic_test Interleukin-6 Tumor Necrosis Factor-alpha Macrophages NF-kappa B NF-κB General Medicine Hypoxia-Inducible Factor 1 alpha Subunit equipment and supplies Cell biology chemistry Tumor necrosis factor alpha medicine.symptom Heme Oxygenase-1 |
| Zdroj: | Biochimie. 112:187-195 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/j.biochi.2015.03.009 |
| Popis: | The transcription factor HIF-1α regulates the adaptive response of cells to hypoxia and oxidative stress. In addition, an important regulatory role for HIF-1α in immune reactions and inflammation is suggested. The present study attempts to investigate the effect of the gaseous signalling molecule hydrogen sulphide (H2S) on HIF-1α in THP-1 macrophages using the slow H2S releasing donor GYY4137. We found that H2S induced HIF-1α protein accumulation in THP-1 macrophages in a concentration-dependent manner. Western blot analysis of cell fractions showed that HIF-1α protein translocates into the nucleus and leads to an increase of its target protein glucose transporter-1 (GLUT-1). Activation of nuclear factor-κB (NF-κB), as well as secretion of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were reduced in the presence of H2S. These findings indicate that HIF-1α accumulation due to H2S was not triggered by the NF-κB pathway. The antioxidant pathway Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/heme oxygenase-1) was activated by H2S. Inhibition of the p38 mitogen-activated protein kinase (MAPK) reversed H2S mediated effects, suggesting that the p38 MAPK pathway may be involved in H2S induced HIF-1α/Nrf2 signalling pathways. |
| Databáze: | OpenAIRE |
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