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O-Acetylation of GD3 Prevents its Apoptotic Effect and Promotes Survival of Lymphoblasts in Childhood Acute Lymphoblastic Leukaemia

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Title O-Acetylation of GD3 Prevents its Apoptotic Effect and
Promotes Survival of Lymphoblasts in Childhood Acute
Lymphoblastic Leukaemia
 
Creator Mukherjee, Kankana
Chava, Anil Kumar
Mandal, Chandan
Dey, Sailendra Nath
Kniep, Bernhard
Chandra, Sarmila
Mandal, Chitra
 
Subject Infectious Diseases and Immunology
 
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.
 
Date 2008
 
Type Article
PeerReviewed
 
Format application/pdf
 
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.
 
Relation http://dx.doi.org/10.1002/jcb.21867
http://www.eprints.iicb.res.in/170/