Sulfatide does not induce apoptosis in arylsulfatase A‐deficient cells

Abstract

Deficiency of arylsulfatase A (ASA) causes metachromatic leukodystrophy (MLD). Patients suffering from this inherited disease show reduced or complete loss of ability to degrade sulfatide. Sulfatide is an abundant lipid of mammalian cellular membrances and preferentially localised in brain tissue. Neurological symptoms of MLD‐patients, therefore, may be caused by increased amoounts of cellular sulfatide. In the present study I have tested this idea by treating various cell lines with sulfatide and examining the rate of apoptosis. Four mammalian cell lines including the mouse glial cell lines 11+/+C1 and ASA‐deficient 17–/–A1 have been used. I show that exogenously applied sulfatide was incorporated and intracellularly stored in these cells. Incorporation of sulfatide was at a lower level in the presence of recombinant ASA. FACS analysis of propidiumiodide stained cells revealed that treatment of cells with sulfatide had no effect on apoptosis.

Deletion of fatty acid amide hydrolase reduces lyso-sulfatide levels but exacerbates metachromatic leukodystrophy in mice

“…To evaluate the dissemination of fluorescently labeled sulfatide and its breakdown products on a subcellular level, wild-type and ASA-deficient cells were translipofected and analyzed by life-cell fluorescence microscopy. For this purpose we used two astrocytoma cell lines derived from wild-type mouse brain (11+/+C1) and ASA-knockout mouse brain (17−/−A1), respectively ( 13 ). To circumvent the low photostability of NBD, making long-term in vivo imaging difficult, sulfatide carrying an N-linked fatty acid with a more stable BODIPY 500/510 fluorophore (green) was synthesized ( 14 ).…”

“…Two immortalized astrocytoma cell lines, wildtype 11+/+C1 cells and ASA-deficient 17-/-A1 cells, were used (13). Unless otherwise indicated they were cultured in Dulbecco's modified eagle medium (DMEM) without phenol red (Thermo Fisher Scientific, Rockford, USA, cat.…”