title: Signaling effects of sodium hydrosulfide in healthy donor peripheral blood mononuclear cells.
abstract: Hydrogen sulfide (H2S) is an endogenous gasotransmitter in human physiology and inflammatory disease, however, with limited knowledge of how signal transduction pathways are involved in immune cells. To examine the effects of sulfide on relevant intracellular signaling in human peripheral blood mononuclear cells (PBMCs), we stimulated healthy donor PBMCs with sodium hydrosulfide (NaHS, 1-1000μM) to mimic H2S stimulation, and analyzed phosphorylation of p38 mitogen activated protein kinase (MAPK) (pT180/pY182), NF-κB p65 (pS529), Akt (pS473) and CREB/ATF1 (pS133/pS63) with flow and mass cytometry. In contrast to transient effects in subsets of lymphocytes, classical monocytes demonstrated sustained phosphorylation of p38, Akt and CREB/ATF1. NaHS induced calcium dependent phosphorylation of p38, Akt and CREB, but not NF-κB, and the phosphorylation of Akt was partly dependent on p38, indicative of p38-Akt crosstalk. Attenuation of these effects by molecules targeting p38 and Hsp90 indicated Hsp90 as a possible target for H2S-induced activation of p38. These results provide a description of a NaHS-induced signal transduction pathway in human primary immune cells that may have relevance for the role of sulfides in inflammation.
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: André
authors.initials: A
authors.lastname: Sulen
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Stein-Erik
authors.initials: SE
authors.lastname: Gullaksen
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Bergen Group of Epidemiology and Biomarkers in Rheumatic Disease (BEaBIRD), Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Lucius
authors.initials: L
authors.lastname: Bader
authors.affiliation: Biotechnology Centre of Oslo, University of Oslo, Norway.
authors.forename: David W
authors.initials: DW
authors.lastname: McClymont
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Jørn
authors.initials: J
authors.lastname: Skavland
authors.affiliation: Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway; Neuroimmunology Lab, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Sonia
authors.initials: S
authors.lastname: Gavasso
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway. Electronic address: bjorn.gjertsen@uib.no.
authors.forename: Bjørn T
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013440:Sulfides / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018841:HSP90 Heat-Shock Proteins; D016328:NF-kappa B; D013440:Sulfides; D051996:Transcription Factor RelA; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
keywords: BAPTA-AM (PubChem CID: 2293); BIRB796 (PubChem CID: 156422); BRL 50481 (PubChem CID: 2921148); Calcium; Chelerythrine chloride (PubChem CID: 72311); Geldanamycin (PubChem CID: 5288382); H-89 dihydrochloride (PubChem CID: 5702541); Hydrogen sulfide (H(2)S); Intracellular signaling; Mibefradil dihydrochloride (PubChem CID: 60662); P38 mitogen activated protein kinase (MAPK); PH-797804 (PubChem CID: 22049997); Phospho-specific antibodies; Small molecule inhibitors; Sodium hydrosulfide (PubChem CID: 28015)