O-Acetylation of GD3 Prevents its Apoptotic Effect and Promotes Survival of Lymphoblasts in Childhood Acute Lymphoblastic Leukaemia
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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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, Kankana
Chava, Anil Kumar Mandal, Chandan Dey, Sailendra Nath Kniep, Bernhard Chandra, Sarmila Mandal, Chitra |
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| Subject |
Infectious Diseases and Immunology
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| Description |
We have previously demonstrated induction ofO-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-Oacetylation
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 thatO-acetylation of GD3, like that ofO-acetylated sialoglycoproteins, might be a general strategy adopted by leukaemic blasts
towards survival in ALL. J. Cell. Biochem. 105: 724–734, 2008. � 2008 Wiley-Liss, Inc.
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| Date |
2008
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/170/1/JOURNAL_OF_CELLULAR_BIOCHEMISTRY%2C105(3)%2C724%2D734%2C2008[24].pdf
Mukherjee, Kankana and Chava, Anil Kumar and Mandal, Chandan and Dey, Sailendra Nath and Kniep, Bernhard and Chandra, Sarmila and Mandal, Chitra (2008) O-Acetylation of GD3 Prevents its Apoptotic Effect and Promotes Survival of Lymphoblasts in Childhood Acute Lymphoblastic Leukaemia. Journal of Cellular Biochemistry, 105 (3). pp. 724-734. |
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| Relation |
http://dx.doi.org/10.1002/jcb.21867
http://www.eprints.iicb.res.in/170/ |
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