Glucosamine prevents polarization of cytotoxic granules in NK-92 cells by disturbing FOXO1/ERK/paxillin phosphorylation

PloS One
Janja BožičIztok Dolenc

Abstract

Glucosamine (GlcN) is a naturally occurring derivative of glucose and an over-the-counter food additive. However, the mechanism underlying GlcN action on cells is unknown. In this study, we investigated the effect of GlcN on natural killer (NK) cells. We demonstrate that GlcN affects NK-92 cell cytotoxicity by altering the distribution of cathepsin C, a cysteine protease required for granzyme processing in cytotoxic granules. The relocation of cathepsin C due to GlcN was shown to be accompanied by a decrease in the intracellular enzyme activity and its extracellular secretion. Similarly, the relocation of endosomal aspartic cathepsin E was observed. Furthermore, we elucidated that repositioning of cathepsin C is a consequence of altered signaling pathways of cytotoxic granule movement. The inhibition of phosphorylation upstream and downstream of ERK by GlcN disturbed the polarized release of cytotoxic vesicles. Considerable changes in the ERK phosphorylation dynamics, but not in those of p38 kinase or JNK, were observed in the IL2-activated NK-92 cells. We found decreased phosphorylation of the transcription factor FOXO1 and simultaneous prolonged phosphorylation of ERK as well as its nuclear translocation. Additionally, a prot...Continue Reading

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Citations

May 1, 2020·Journal of Biomedical Science·Yi-Hsuan ChangKuo-I Lin

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Methods Mentioned

BETA
fluorescence-activated cell sorter
electrophoresis
confocal microscopy
nuclear translocation
fluorescence microscopy
nuclear
immunoprecipitation

Software Mentioned

Corel Draw
Leica LAS
Excel
ImageJ
LAS AF
Cellquest

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