title: Fe2O3 nanoparticles suppress Kv1.3 channels via affecting the redox activity of Kvβ2 subunit in Jurkat T cells.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are promising nanomaterials in medical practice due to their special magnetic characteristics and nanoscale size. However, their potential impacts on immune cells are not well documented. This study aims to investigate the effects of Fe2O3 nanoparticles (Fe2O3-NPs) on the electrophysiology of Kv1.3 channels in Jurkat T cells. Using the whole-cell patch-clamp technique, we demonstrate that incubation of Jurkat cells with Fe2O3-NPs dose- and time-dependently decreased the current density and shifted the steady-state inactivation curve and the recovery curve of Kv1.3 channels to a rightward direction. Fe2O3-NPs increased the NADP level but decreased the NADPH level of Jurkat cells. Direct induction of NADPH into the cytosole of Jurkat cells via the pipette abolished the rightward shift of the inactivation curve. In addition, transmission electron microscopy showed that Fe2O3-NPs could be endocytosed by Jurkat cells with relatively low speed and capacity. Fe2O3-NPs did not significantly affect the viability of Jurkat cells, but suppressed the expressions of certain cytokines (TNFα, IFNγ and IL-2) and interferon responsive genes (IRF-1 and PIM-1), and the time courses of Fe2O3-NPs endocytosis and effects on the expressions of cytokines and interferon responsive genes were compatible. We conclude that Fe2O3-NPs can be endocytosed by Jurkat cells and act intracellularly. Fe2O3-NPs decrease the current density and delay the inactivation and recovery kinetics of Kv1.3 channels in Jurkat cells by oxidizing NADPH and therefore disrupting the redox activity of the Kvβ2 auxiliary subunit, and as a result, lead to changes of the Kv1.3 channel function. These results suggest that iron oxide nanoparticles may affect T cell function by disturbing the activity of Kv1.3 channels. Further, the suppressing effects of Fe2O3-NPs on the expressions of certain inflammatory cytokines and interferon responsive genes suggest that iron oxide nanoparticles may exert modulatory effects on T cell immune activities and anti-inflammation effects.
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Liu
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Tan
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Cao
mesh_terms: D016207:Cytokines / Q000378:metabolism; D004705:Endocytosis; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007372:Interferons / Q000235:genetics; D019169:Jurkat Cells; D051664:Kv1.3 Potassium Channel / Q000378:metabolism* / Q000502:physiology; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010084:Oxidation-Reduction; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051637:Shaker Superfamily of Potassium Channels
chemical_list: D016207:Cytokines; D005290:Ferric Compounds; C498948:KCNAB2 protein, human; D051664:Kv1.3 Potassium Channel; D058185:Magnetite Nanoparticles; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels; C000499:ferric oxide; D007372:Interferons