title: The association between oxidative stress-induced galectins and differentiation of human promyelocytic HL-60 cells.
abstract: Galectins are multifunctional β-galactoside-binding proteins that are involved in the regulation of cellular stress responses and differentiation. The relationship between these processes is unclear and we report here that galectins display oxidative-stress specific expression patterns in neutrophil-like differentiated HL-60 cells. Three galectins (-1, -3, and -10) are upregulated in response to either menadione or DMSO exposure whereas galectins -9 and -12 exhibited a stimulus-dependent downregulation. Changes in galectin expression are oxidant dependent based on the observations that 1) oxidative stress biomarkers HMOX1 (heme oxygenase-1) and NCF1 (neutrophil cytosolic factor 1, which is also a biomarker of neutrophil differentiation) are elevated in both cases, and 2) the antioxidant N-acetyl-L-cysteine restores basal expression of galectin-3 following oxidant exposure. In addition, our results suggest that the regulation of oxidative stress-sensitive galectins involves DNA hypomethylation mechanisms. Expression of galectin-3 and galectin-12 exhibits an opposite relationship to the expression of HMOX1/NCF1, suggesting a stimulatory and inhibitory role of these galectins in neutrophil-like differentiation of HL-60 cells. We also show that the inhibition of galectins reduces the growth rate of HL-60 cells, and facilitates their neutrophil-like differentiation. Collectively, our findings indicate that the process of cellular differentiation implicates, in part, oxidative stress-sensitive galectins, which further highlights a biological significance of galectin network remodeling in cells.
authors.affiliation: Department of Biology, The University of Western Ontario, London, ON, Canada, N6A 5B7.
authors.forename: James R
authors.initials: JR
authors.lastname: Vinnai
authors.affiliation: Department of Biology, The University of Western Ontario, London, ON, Canada, N6A 5B7.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Cumming
authors.affiliation: Department of Biology, The University of Western Ontario, London, ON, Canada, N6A 5B7.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Thompson
authors.affiliation: Department of Biology, The University of Western Ontario, London, ON, Canada, N6A 5B7. Electronic address: atimoshe@uwo.ca.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Timoshenko
mesh_terms: D047250:Calixarenes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004187:Disaccharides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D037161:Galectins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007785:Lactose / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D013329:Structure-Activity Relationship; D013862:Thiogalactosides / Q000494:pharmacology; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D004187:Disaccharides; D037161:Galectins; D013862:Thiogalactosides; C530377:compound 0118; D047250:Calixarenes; C005608:lactobionic acid; D024483:Vitamin K 3; C031803:thiodigalactoside; D007785:Lactose
keywords: Cell differentiation; Cell proliferation; DNA hypomethylation; Galectins; Hydrogen peroxide; JNK signaling; Leukemia; Menadione; Oxidative stress