ChemInform Abstract: Preparation of Radiolabeled Gangliosides

Sonnino, Sandro; Nicolini, M.; Chigorno, Vanna

doi:10.1002/chin.199709240

Cited by 11 publications

(15 citation statements)

References 1 publication

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“…Ganglioside GD1a was purified from the total ganglioside mixture extracted and purified from the bovine brain. 37 Radioactive GD1a containing erythro-C18-sphingosine, isotopically tritium labeled at position 3 ([3-3 H(Sph18)]GD1a), was prepared according to Sonnino et al 37 and purified by reversed-phase HPLC (homogeneity over 99%; specific radioactivity, 1.2 Ci/mmol). 38 Cell culture and stable silencing of Neu3 in K562 cells.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K562 through the increase of ganglioside GM3

et al. 2008

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In chronic myeloid leukemia K562 cells, differentiation is also blocked because of low levels of ganglioside GM3, derived by the high expression of sialidase Neu3 active on GM3. In this article, we studied the effects of Neu3 silencing (40-70% and 63-93% decrease in protein content and activity, respectively) in these cells. The effects were as follows: (a) gangliosides GM3, GM1, and sialosylnorhexaosylceramide increased markedly; (b) cell growth and [3 H]thymidine incorporation diminished relevantly; (c) as mRNA, cyclin D2, and Myc were much less expressed, whereas cyclin D1 was expressed more like its inhibitor p21; (d) as mRNA, pro-apoptotic proteins Bax and Bad increased with concurrent decrease and increase in the anti-apoptotic proteins Bcl-2 and Bcl-XL, respectively; (e) the apoptosis inducers etoposide and staurosporine were active on Neu3 silencing cells but not on mock cells; (f) as mRNA, the megakaryocytic markers CD10, CD44, CD41, and CD61 increased similar to the case of mock cells stimulated with PMA; (g) the signaling cascades mediated by PLC-b2, PKC, RAF, ERK1/2, RSK90, and JNK were largely activated. The induction of a GM3-rich ganglioside pattern in K562 cells by treatment with brefeldin A elicited a phenotype similar to that of Neu3 silencing cells. In conclusion, upon Neu3 silencing, K562 cells show a decrease in proliferation, propensity to undergo apoptosis, and megakaryocytic differentiation.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K562 through the increase of ganglioside GM3

et al. 2008

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“…GD1a Enrichment of CA-TC Cells-To enrich for GD1a content, the CA-TC cells were cultivated in Optimem I medium (Invitrogen) containing 50 M GD1a that was purified from a total ganglioside mixture extracted from bovine brain (17). The cells were incubated for 48 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

The Plasma Membrane Sialidase NEU3 Regulates the Malignancy of Renal Carcinoma Cells by Controlling β1 Integrin Internalization and Recycling

Tringali

Lupo

Silvestri

et al. 2012

Journal of Biological Chemistry

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Background: NEU3 is involved in ganglioside surface metabolism and is up-regulated in renal carcinoma cells. Results: NEU3 regulates ␤1 integrin trafficking and the downstream FAK/AKT pathway, influencing drug resistance and invasive potential. Conclusion: NEU3 is a key regulator of renal cell carcinoma malignancy. Significance: NEU3 could be a new target for molecular therapies for renal carcinoma.

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“…2′‐(4‐methylumbelliferyl)‐α‐ D ‐ N ‐acetylneuraminic acid (4‐MU‐NeuAc), 4‐methylumbelliferone (MU) and 3,3′‐diaminobenzidine (DAB) were from Sigma (St. Louis, MO). [3‐ 3 H]sphingosine was from Perkin Elmer (Waltham, MA); [ 3 H]GD1a were prepared by dichloro‐dicyano‐benzoquinone/sodium boro[ 3 H]hydride method followed by reverse phase HPLC purification 37. Anti‐Neu3 antibody was the kind gift from Dr. Stamatos M. Nicholas, University of Maryland Medical Center, Baltimore, MD.…”

Section: Methodsmentioning

confidence: 99%

Down regulation of membrane‐bound Neu3 constitutes a new potential marker for childhood acute lymphoblastic leukemia and induces apoptosis suppression of neoplastic cells

Mandal

Tringali

Mondal

et al. 2009

Intl Journal of Cancer

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Membrane-linked sialidase Neu3 is a key enzyme for the extralysosomal catabolism of gangliosides. In this respect, it regulates pivotal cell surface events, including trans-membrane signaling, and plays an essential role in carcinogenesis. In this report, we demonstrated that acute lymphoblastic leukemia (ALL), lymphoblasts (primary cells from patients and cell lines) are characterized by a marked down-regulation of Neu3 in terms of both gene expression (230 to 40%) and enzymatic activity toward ganglioside GD1a (225.6 to 30.6%), when compared with cells from healthy controls. Induced overexpression of Neu3 in the ALL-cell line, MOLT-4, led to a significant increase of ceramide (166%) and to a parallel decrease of lactosylceramide (255%). These events strongly guided lymphoblasts to apoptosis, as we assessed by the decrease in Bcl2/ Bax ratio, the accumulation of Neu3 transfected cells in the sub G0-G1 phase of the cell cycle, the enhanced annexin-V positivity, the higher cleavage of procaspase-3. Therefore, the reduced expression of Neu3 in ALL could help lymphoblasts to survive, maintaining the cellular content of ceramide below a critical level. Interestingly, we found that Neu3 activity varied in relation to disease progression, increasing in clinical remission after chemotherapy, and decreasing again in patients that relapsed. In addition, a negative correlation was observed between Neu3 expression and the percentage of the ALL marker 9-OAcGD3 positive cells. Consequently, Neu3 could represent a new potent biomarker in childhood ALL, to assess the efficacy of therapeutic protocols and to rapidly identify an eventual relapse.

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ChemInform Abstract: Preparation of Radiolabeled Gangliosides

Cited by 11 publications

References 1 publication

RETRACTED ARTICLE: Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K562 through the increase of ganglioside GM3

RETRACTED ARTICLE: Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K562 through the increase of ganglioside GM3

The Plasma Membrane Sialidase NEU3 Regulates the Malignancy of Renal Carcinoma Cells by Controlling β1 Integrin Internalization and Recycling

Down regulation of membrane‐bound Neu3 constitutes a new potential marker for childhood acute lymphoblastic leukemia and induces apoptosis suppression of neoplastic cells

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