Human oligodendrocyte MO3.13 cells & Globoid cell leukodystrophy

In this paper (Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death), Voccoli et al. used Human oligodendrocyte MO3.13 cells to study Globoid cell leukodystrophy.

Globoid cell leukodystrophy (GLD) is a metabolic disease caused by mutations in the galactocerebrosidase (GALC) gene. GALC is a lysosomal enzyme whose function is to degrade galacto-lipids, including galactosyl-ceramide and galactosyl-sphingosine (psychosine, PSY). GALC loss of function causes progressive intracellular accumulation of PSY. It is widely held that PSY is the main trigger for the degeneration of myelinating cells and progressive white-matter loss. However, still little is known about the molecular mechanisms by which PSY imparts toxicity. In this paper, the role of calcium dynamics during PSY-induced cell death is addressed. Using the human oligodendrocyte cell line MO3.13, the authors report that cell death by PSY is accompanied by robust cytosolic and mitochondrial calcium (Ca²⁺) elevations, and by mitochondrial reactive oxygen species (ROS) production. Importantly, they demonstrate that the reduction of extracellular calcium content by the chelating agent ethylenediaminetetraacetic acid can decrease intra-mitochondrial ROS production and enhance cell viability. Antioxidant administration also reduces mitochondrial ROS production and cell loss, but this treatment does not synergize with Ca²⁺ chelation. Their results disclose novel intracellular pathways involved in PSY-induced death that may be exploited for therapeutic purposes to delay GLD onset and/or slow down its progression.

V Voccoli¹, I Tonazzini¹, G Signore², M Caleo³ and M Cecchini¹