Glycobiology Advance Access originally published online on December 29, 2004
Glycobiology 2005 15(6):585-591; doi:10.1093/glycob/cwi039
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Glycobiology vol. 15 no. 6 © Oxford University Press 2004; all rights reserved.
Involvement of gangliosides in glucosamine-induced proliferation decrease of retinal pericytes
Diabetic Microangiopathy Research Unit, Merck Santé-INSERM UMR 585, INSA-Lyon, Louis Pasteur Bldg, 69621 Villeurbanne Cedex, France
1 To whom correspondence should be addressed; e-mail: samer.elbawab{at}merck.fr
Received on July 15, 2004; revised on December 20, 2004; accepted on December 23, 2004
The hexosamine pathway (HP) is a biochemical hypothesis recently proposed explaining cellular alterations occurring during diabetic microvascular complications. Diabetic retinopathy is a common microvascular complication of diabetes, and it is known that cell proliferation is severely affected during the development of the disease. Particularly, early stages are characterized by death of the retinal microvascular cells, pericytes. Gangliosides have often been described to regulate cell growth; however, very few studies focused on the potential role of gangliosides in diabetic microvascular alterations. The aim of this article was to investigate the effect of the HP activation on pericyte proliferation and determine the potential implication of gangliosides in this process. Results indicate first that HP activation, mimicked by glucosamine treatment, decreased pericyte proliferation. Second, glucosamine treatment induced a modification of gangliosides pattern, particularly GM1 and GD3 were significantly increased. Next, results showed that exogenous addition of a-series gangliosides (GM3, GM2, GM1, GD1a) and b-series ganglioside (GD3) caused a decrease of pericyte proliferation, whereas nonsialylated precursors glucosylceramide and lactosylceramide were without effect. Furthermore, when ganglioside biosynthesis was blocked using PPMP, a glucosylceramide synthase inhibitor, the effects of glucosamine on pericyte proliferation were partially reversed. Our results suggest that in retinal pericytes, gangliosides and particularly GM1 and GD3 that are increased in response to glucosamine, are involved in the antiproliferative effect of glucosamine. These observations also underlie the potential involvement of gangliosides in a pathological context, such as diabetic microvascular complications.
Key words: diabetic retinopathy / gangliosides / hexosamine pathway / pericytes
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