Hydrogen sulphide induces HIF-1α and Nrf2 in THP-1 macrophages

The transcription factor HIF-1 alpha regulates the adaptive response of cells to hypoxia and oxidative stress. In addition, an important regulatory role for HIF-1 alpha 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-1 alpha in THP-1 macrophages using the slow H2S releasing donor GYY4137. We found that H2S induced HIF-1 alpha protein accumulation in THP-1 macrophages in a concentration-dependent manner. Western blot analysis of cell fractions showed that HIF-1 alpha protein translocates into the nucleus and leads to an increase of its target protein glucose transporter-1 (GLUT-1). Activation of nuclear factor-kappa B (NF-kappa B), as well as secretion of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), were reduced in the presence of H2S. These findings indicate that HIF-1 alpha accumulation due to H2S was not triggered by the NF-kappa B 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-1 alpha/Nrf2 signalling pathways. (C) 2015 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.