title: NADPH oxidase-dependent production of reactive oxygen species induces endoplasmatic reticulum stress in neutrophil-like HL60 cells.
abstract: Reactive oxygen species (ROS) primarily produced via NADPH oxidase play an important role for killing microorganisms in neutrophils. In this study we examined if ROS production in Human promyelocytic leukemia cells (HL60) differentiated into neutrophil-like cells (dHL60) induces ER stress and activates the unfolded protein response (UPR). To cause ROS production cells were treated with PMA or by chronic hyperglycemia. Chronic hyperglycemia failed to induce ROS production and did not cause activation of the UPR in dHL60 cells. PMA, a pharmacologic NADPH oxidase activator, induced ER stress in dHL60 cells as monitored by IRE-1 and PERK pathway activation, and this was independent of calcium signaling. The NADPH oxidase inhibitor, DPI, abolished both ROS production and UPR activation. These results show that ROS produced by NADPH oxidase induces ER stress and suggests a close association between the redox state of the cell and the activation of the UPR in neutrophil-like HL60 cells.
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Wilson Mitsuo Tatagiba
authors: WM
authors: Kuwabara
authors: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors: Liling
authors: L
authors: Zhang
authors: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors: Irmgard
authors: I
authors: Schuiki
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Rui
authors: R
authors: Curi
authors: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors: Allen
authors: A
authors: Volchuk
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Tatiana Carolina
authors: TC
authors: Alba-Loureiro
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium