Sulfation of keratan sulfate proteoglycan reduces radiation‐induced apoptosis in human Burkitt's lymphoma cell lines

Abstract

Edited by Vladimir SkulachevKeywords: Apoptosis Burkitt's lymphoma Keratan sulfate PAPST Radiation a b s t r a c t This study focuses on clarifying the contribution of sulfation to radiation-induced apoptosis in human Burkitt's lymphoma cell lines, using 3 0 -phosphoadenosine 5 0 -phosphosulfate transporters (PAPSTs). Overexpression of PAPST1 or PAPST2 reduced radiation-induced apoptosis in Namalwa cells, whereas the repression of PAPST1 expression enhanced apoptosis. Inhibition of PAPST slightly decreased keratan sulfate (KS) expression, so that depletion of KS significantly increased radiationinduced apoptosis. In addition, the repression of all three N-acetylglucosamine-6-O-sulfotransferases (CHST2, CHST6, and CHST7) increased apoptosis. In contrast, PAPST1 expression promoted the phosphorylation of p38 MAPK and Akt in irradiated Namalwa cells. These findings suggest that 6-O-sulfation of GlcNAc residues in KS reduces radiation-induced apoptosis of human Burkitt's lymphoma cells.

Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

“…CS is composed of repeating disaccharides of N-acetylgalactosamine (GalNAc) and Dglucuronic acid (GlcA) with different sulfation patterns, mediated by various specific CHSTs: [6,9,15,18,21,23]. CHST9 catalyzes mainly the transfer of sulfate to position 4 of terminal N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans [14] (Fig.…”

SLC35B2 Expression is Associated with a Poor Prognosis of Invasive Ductal Breast Carcinoma

“…The SLC35B2 gene also plays an important role in cancer-cell proliferation, by controlling their sulfation status as part of a desmoplastic reaction to support cancer growth in colorectal cancers (Kamiyama et al, 2011). Furthermore, over-expression of PAPST 1 or PAPST 2 reduced radiation-induced apoptosis in human Burkitt's lymphoma cells (Nakayama et al, 2013). This study showed that increased levels of SLC35B2 mRNA in invasive ductal breast carcinomas are associated with advanced-stage breast cancer.…”

Keratan sulfate: An up-to-date review

“…The study of Nakayama and coworkers has shown the contribution of KSPGs, and its sulfation content to radio-resistance in human Burkitt's lymphoma cellular apoptotic process [22]. The authors have induced apoptosis in Burkitt's lymphoma cell lines by X-ray radiation at a dose rate of approximately 2.4 Gy/min.…”

“…Enzymatic therapy using KS-related degrading enzymes is a route to fight this pathology. [22] Mucopolysaccharidosis…”

“…Since KS is inadequately deposited in patients of MPS IVA due to dysfunction of the galactose 6-sulfate sulfatase, it has been reported that measurements of the accumulated mutation on the gene GALNS of this enzyme, as well as the plasma and blood KS concentrations, are quite useful to the diagnostic of the severity levels of this disease. Curiously, all works available in the literature between 2010 and 2014 concerning the beneficial roles of KS to health or as target molecule for therapeutic purpose come from Japan [19][20][21][22][23]. These works have been revisited in the second topic (Section 3) of this review, and are describing the potential roles of KS in suppressing the cartilage damage, in combating inflammation process, in reducing radiation-induced apoptosis of lymphoma cells, and in suppressing early phase pathogenesis of ALS.…”