O-Acetylation of GD3 Prevents its Apoptotic Effect and Promotes Survival of Lymphoblasts in Childhood Acute Lymphoblastic Leukaemia
Metadata of CSIR Papers
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| Title |
O-Acetylation of GD3 Prevents its Apoptotic Effect and Promotes Survival of Lymphoblasts in Childhood Acute Lymphoblastic Leukaemia
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| Creator |
Mukherjee, K
Chava, AK Mandal, C Dey, SN Kniep, B Chandra, S Mandal, C |
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| Subject |
Biochemistry & Molecular Biology; Cell Biology
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| Description |
We have previously demonstrated induction of O-acetylated sialoglycoproteins on lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). These molecules promote survival of lymphoblasts by preventing apoptosis. Although O-acetylated sialoglycoproteins are over expressed, the status of O-acetylation of gangliosides and their role in lymphoblasts survival remains to be explored in ALL patients. Here, we have observed enhanced levels of 9-O-acetylated GD3 (9-O-AcGD3) in the lymphoblasts of patients and leukaemic cell line versus disialoganglioside GD3 in comparison to the normal cells. Localization of GD3 and 9-O-AcGD3 on mitochondria of patient's lymphoblasts has been demonstrated by immuno-electron microscopy. The exogenous administration of GD3-induced apoptosis in lymphoblasts as evident from the nuclear fragmentation and sub G0/G1 apoptotic peak. In contrast, 9-O-AcGD3 failed to induce such apoptosis. We further explored the mitochondria-dependent pathway triggered during GD3-induced apoptosis in lymphoblasts. GD3 caused a time-dependent depolarization of mitochondrial membrane potential, release of cytochrome c and 7.4- and 8-fold increased in caspase 9 and caspase 3 activity respectively. However, under identical conditions, an equimolar concentration of 9-O-AcGD3 failed to induce similar effects. Interestingly, 9-O-AcGD3 protected the lymphoblasts from GD3-induced apoptosis when administered in equimolar concentrations simultaneously. In situ de-O-acetylation of 9-O-AcGD3 with sodium salicylate restores the GD3-responsiveness to apoptotic signals. Although both GD3 and 9-O-acetyl GD3 localize to mitochondria, these two structurally related molecules may play different roles in ALL-disease biology. Taken together, our results suggest that O-acetylation of GD3, like that of O-acetylated sialoglycoproteins, might be a general strategy adopted by leukaemic blasts towards survival in ALL. J. Cell. Biochem. 105: 724-734, 2008. (c) 2008 Wiley-Liss, Inc.
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| Publisher |
WILEY-LISSHOBOKENDIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
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| Date |
2011-09-20T12:12:44Z
2011-09-20T12:12:44Z 2008 |
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| Type |
Article
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| Identifier |
JOURNAL OF CELLULAR BIOCHEMISTRY
0730-2312 http://hdl.handle.net/123456789/14403 |
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| Language |
English
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