title: Hydrogen sulphide induces HIF-1α and Nrf2 in THP-1 macrophages.
abstract: 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.
authors: Center of Pathobiochemistry and Genetics, Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Vienna, Austria.
authors: Lilian
authors: L
authors: Lohninger
authors: Center of Pathobiochemistry and Genetics, Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Vienna, Austria; Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic; Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors: Lenka
authors: L
authors: Tomasova
authors: Center of Pathobiochemistry and Genetics, Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Vienna, Austria.
authors: Monika
authors: M
authors: Praschberger
authors: Division of Drug Design and Medicinal Chemistry, Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Hintersteininger
authors: Division of Drug Design and Medicinal Chemistry, Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors: Thomas
authors: T
authors: Erker
authors: Center of Pathobiochemistry and Genetics, Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Vienna, Austria.
authors: Bernhard M K
authors: BM
authors: Gmeiner
authors: Center of Pathobiochemistry and Genetics, Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Vienna, Austria. Electronic address: hildegard.laggner@meduniwien.ac.at.
authors: Hilde
authors: H
authors: Laggner
mesh_terms: D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508600:IL6 protein, human; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D014409:Tumor Necrosis Factor-alpha; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D006862:Hydrogen Sulfide
keywords: GYY4137; H(2)S; Heme oxygenase-1; NF-κB; p38 MAPK