The Recognition of N-Glycans by the Lectin ArtinM Mediates Cell Death of a Human Myeloid Leukemia Cell Line

Autor(es)

Carvalho, Fernanda Caroline ^[1] ; Soares, Sandro Gomes ^[2] ; Tamarozzi, Mirela Barros ^[2] ; Rego, Eduardo Magalhaes ^[3] ; Roque-Barreira, Maria-Cristina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Sao Paulo - Brazil

^[2] Invent Biotecnol Ltda, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 6, n. 11, p. e27892, 2011.
• Citações Web of Science: 17

Resumo

ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus (jackfruit), interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Man alpha 1-3(Man alpha 1-6)Man beta 1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC50 = 10 mu g/mL), as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a beta 1,6-GlcNAc branch linked to alpha 1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a beta 1,6-GlcNAc branch linked to alpha 1,6-mannose as a novel target for anti-leukemia treatment. (AU)

• Processo FAPESP: 06/60642-2 - Efeitos biológicos e aplicações farmacêuticas de lectinas
• Beneficiário: Maria Cristina Roque Antunes Barreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático