title: Regulation of O-acetylation of sialic acids by sialate-O-acetyltransferase and sialate-O-acetylesterase activities in childhood acute lymphoblastic leukemia.
abstract: Enhanced expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)-GPs) and 9-O-acetylated disialoganglioside (9-OAcGD3) was observed on lymphoblasts of childhood acute lymphoblastic leukemia (ALL). Sialate-O-acetyltransferase (SOAT) and sialate-O-acetylesterase (SIAE) are the two main enzymes responsible for the quantity of the O-acetyl ester groups on sialic acids (Sias). We have earlier shown an enhanced level of SOAT activity, capable of transferring acetyl groups to Sias of glycoconjugates in the microsomes of lymphoblasts of these children. We further observed a decreased SIAE activity in both lysosomal and cytosolic fractions of ALL cell lines and primary cells from bone marrow of patients compared with peripheral blood mononuclear cells from healthy donors, which preferentially hydrolyze O-acetyl groups at C-9 of Sia. The level of O-acetylated Sias in the cytosolic and the lysosomal fractions showed a good correlation with SIAE activity in the corresponding fractions. The apparent K(M) values for SIAE in the lysosomal and the cytosolic fractions from lymphoblasts of ALL patients are 0.38 and 0.39 mM, respectively. These studies demonstrate that both SIAE and SOAT activities seem to be responsible for the enhanced level of Neu5,9Ac(2) in lymphoblasts, which is a hallmark in ALL. This was subsequently confirmed by using an enzyme-linked immunosorbent assay that also demonstrated a steady decline in SOAT activities even in cell lysates of lymphoblasts during successful chemotherapy, like radioactive methods have shown earlier.
authors.affiliation: Cancer and Cell Biology Division, Council of Scientific and Industrial Research, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata700032, India.
authors.forename: Chandan
authors.initials: C
authors.lastname: Mandal
authors.forename: Chhabinath
authors.initials: C
authors.lastname: Mandal
authors.forename: Sarmila
authors.initials: S
authors.lastname: Chandra
authors.forename: Roland
authors.initials: R
authors.lastname: Schauer
authors.forename: Chitra
authors.initials: C
authors.lastname: Mandal
mesh_terms: D000107:Acetylation; D000115:Acetylesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism*; D000293:Adolescent; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D003600:Cytosol / Q000201:enzymology; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006868:Hydrolysis; D007223:Infant; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000201:enzymology*; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism
chemical_list: D005732:Gangliosides; D007527:Isoenzymes; D012794:Sialic Acids; D012795:Sialoglycoproteins; C025447:sialogangliosides; D000217:Acyltransferases; C082760:sialate 9-O-lactoyltransferase; D000115:Acetylesterase; C046298:sialate O-acetylesterase