Phenolic metabolites of benzene induced caspase-dependent cytotoxicities to K562 cells accompanied with decrease in cell surface sialic acids

Abstract

Benzene-induced erythropoietic depression has been proposed to be due to the production of toxic metabolites. Presently, the cytotoxicities of benzene metabolites, including phenol, catechol, hydroquinone, and 1,2,4-benzenetriol, to erythroid progenitor-like K562 cells were investigated. After exposure to these metabolites, K562 cells showed significant inhibition of viability and apoptotic characteristics. Each metabolite caused a significant increase in activities of caspase-3, -8, and -9, and pretreatment with caspase-3, -8, and -9 inhibitors significantly inhibited benzene metabolites-induced phosphatidylserine exposure. These metabolites also elevated expression of Fas and FasL on the cell surface. After exposure to benzene metabolites, K562 cells showed an increase in reactive oxygen species level, and pretreatment with N-acetyl-l-cysteine significantly protected against the cytotoxicity of each metabolite. Interestingly, the control K562 cells and the phenol-exposed cells aggregated together, but the cells exposed to other metabolites were scattered. Further analysis showed that hydroquione, catechol, and 1,2,4-benzenetriol induced a decrease in the cell surface sialic acid levels and an increase in the cell surface sialidase activity, but phenol did not cause any changes in sialic acid levels and sialidase activity. Consistently, an increase in expression level of sialidase Neu3 mRNA and a decrease in mRNA level of sialyltransferase ST3GAL3 gene were detected in hydroquione-, catechol-, or 1,2,4-benzenetriol-treated cells, but no change in mRNA levels of two genes were found in phenol-treated cells. In conclusion, these benzene metabolites could induce apoptosis of K562 cells mainly through caspase-8-dependent pathway and ROS production, and sialic acid metabolism might play a role in the apoptotic process.

Increased Level of α2,6-Sialylated Glycans on HaCaT Cells Induced by Titanium Dioxide Nanoparticles under UV Radiation

“…Glycan structure is defined by the expression of nucleotides in the corresponding gene and environmental factors [ 37 ]. Sialylation is an important glycosylation modification that plays an important role in cell signaling [ 38 ], cell adhesion [ 39 ], cell recognition [ 21 ], ageing, and senescence [ 40 ]. Considering the importance of sialylation, we investigated changes in sialylation on HaCaT cells treated with nano-TiO 2 and UV irradiation.…”

The Differential Effect of Cannabidiol on the Composition and Physicochemical Properties of Keratinocyte and Fibroblast Membranes from Psoriatic Patients and Healthy People

“…Regardless of the qualitative and quantitative changes in the structures of phospholipids under the influence of either UVA or UVB radiation, the total level of sialic acid in the membranes of keratinocytes and fibroblasts from healthy people increased in this study. Literature data confirm the relationship between an increase in sialic acid levels and sialylation enhanced by UV [46], which plays an important role in cell signaling [47] and cell adhesion [48]. In contrast, in the case of keratinocytes and fibroblasts exposed to UV radiation from psoriasis patients, the level of sialic acid decreased, which may be related to the induction of apoptosis in response to UV radiation [49].…”

Identification of potential pathways and microRNA-mRNA networks associated with benzene metabolite hydroquinone-induced hematotoxicity in human leukemia K562 cells

“…Activation of CASP3 and CASP8 both have pivotal roles in the execution phase of cell apoptosis. As mentioned, HQ induces apoptosis in HL-60 cells, Jurkat cells, human bone marrow mononuclear cells (BMMNC), and K562 cells accompanied by CASP3 or CASP8 activation [ 7 , 44 , 45 ]. Consistently, HQ exposure markedly upregulated the mRNA levels of CASP3 and CASP8 to 1.53-fold and 1.38-fold of that in the control K562 cells in the present study.…”