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Globotriaosylsphingosine (Lyso-Gb3) or globotriaosylceramide (Gb3)?

Posted by mdsanchez on 01 Aug 2012 at 09:13 GMT

Dear sirs,
This is to kindly draw you attention to the fact that it is unclear what glycolipid species was used by Namdar et al. to load endothelial cells in their manuscript "Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease" (1). The authors state that "Fabry disease is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A resulting in the accumulation of globotriaosylsphingosine (Gb3)". Later, in methods they indicate that Gb3 was obtained from Matreya (Pleasant Gap, PA) and dissolved in chloroform and methanol, air-dried and resuspended in DMSO, then heated and vortexed.
The main glycolipid accumulated in Fabry disease is indeed Gb3. However, this term is used to name globotriaosylceramide. Globotriaosylsphingosine (lyso-Gb3) is a deacylated derivative of globotriaosylceramide (2). Having a fatty acid less that Gb3/globotriaosylceramide, lysoGb3/globotriaosylsphingosine is more soluble. Being more soluble than Gb3, lyso-Gb3 levels are increased in the circulation of Fabry patients (2). Furthermore, lyso-Gb3 preparation procedures for cell culture experiments are facilitated by its increased water solubility when compared to Gb3 (3). We feel that the preparation procedures described by Namdar et al are suggestive of their use of Gb3/globotriaosylceramide, not of lysoGb3/globotriaosylsphingosine (1). In this regard, lyso-Gb3 levels in cell culture medium similar to those found in plasma of Fabry patients promote a fibrogenic response in cultured human podocytes (3). If indeed the authors used globotriaosylceramide (Gb3) we kindly suggest that the title of the manuscript is changed and the correct compound indicated throughout the manuscript.

Maria Dolores Sanchez Niño, PhD, IdIPAZ, Madrid, Spain
Alberto Ortiz, MD, PhD, IIS-Fundacion Jimenez Diaz, Madrid, Spain

1. Namdar M, Gebhard C, Studiger R, Shi Y, Mocharla P, Schmied C, Brugada P, Lüscher TF, Camici GG. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease. PLoS One. 2012;7:e36373

2. Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, van Roomen C, Mirzaian M, Wijburg FA, Linthorst GE, Vedder AC, Rombach SM, Cox-Brinkman J, Somerharju P, Boot RG, Hollak CE, Brady RO, Poorthuis BJ. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA 2008;105:2812-7.

3. Sanchez-Niño MD, Sanz AB, Carrasco S, Saleem MA, Mathieson PW, Valdivielso JM, Ruiz-Ortega M, Egido J, Ortiz A. Globotriaosylsphingosine actions on human glomerular podocytes: implications for Fabry nephropathy. Nephrol Dial Transplant. 2011;26:1797-802

No competing interests declared.

RE: Globotriaosylsphingosine (Lyso-Gb3) or globotriaosylceramide (Gb3)?

nameh-396 replied to mdsanchez on 17 Aug 2012 at 10:48 GMT

Dear colleagues

thank you very much for your interest and the meticulous review of our work. We are well aware of the unfortunate deviation in the title. We used Gb3/globotriaosylceramide.

The correction process is underway.

Best regards

The authors

No competing interests declared.